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<DIV STYLE="text-indent: 0pt; display: block; margin-left: 0pt; margin-right: 0pt; text-align: center">UNITED STATES<font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&nbsp;</FONT></DIV>

<DIV STYLE="text-indent: 0pt; display: block; margin-left: 0pt; margin-right: 0pt; text-align: center"><FONT STYLE="display: inline; font: 10pt times new roman">SECURITIES AND EXCHANGE COMMISSION</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Washington, D.C.&#160;&#160;20549</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">FORM S-8</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">ARQULE, INC.</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(Exact Name of registrant as specified in its charter)</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-SIZE: 10pt">&#160;&#160;&#160;&#160;Delaware&#160;&#160;&#160;&#160;</font></font></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-SIZE: 10pt">&#160;&#160;&#160;&#160;58-1959440&#160;&#160;&#160;&#160;</font></font></div>
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<div><font style="FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(State or other jurisdiction of</font> </font></div>

<div><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">incorporation or organization)</font></div>
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<div><font style="FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(I.R.S. Employer</font> </font></div>

<div><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Identification No.)</font></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">19 Presidential Way,</font></div>

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<td nowrap width="10%" style="BORDER-BOTTOM: black 2px solid; TEXT-ALIGN: center"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Woburn, Massachusetts 01801</font></td>
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<div style="TEXT-ALIGN: center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(Address, including zip code, of principal executive offices)</font></div>

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<td nowrap width="33%" style="BORDER-BOTTOM: black 2px solid; TEXT-ALIGN: center"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">ArQule, Inc. Amended and Restated 1996 Director Stock Option Plan</font></td>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(Full title of the plan)</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Paolo Pucci</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Chief Executive Officer</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">ArQule, Inc.</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">19 Presidential Way,</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Woburn, Massachusetts 01801&#160;&#160;&#160;&#160;</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(781) 994-0300</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(Name, address, including zip code, and telephone number including area code, of agent for service)</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Copy to:</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Richard E. Baltz, Esq.</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">555 12<font style="DISPLAY: inline; FONT-SIZE: 70%; VERTICAL-ALIGN: text-top">th</font> Street, N.W.</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Washington, D.C.&#160;&#160;20004</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(202) 942-5000</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Calculation of Registration Fee</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Title of securities to be </font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">registered</font></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Amount to be </font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Proposed </font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">maximum offering </font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">price per unit (2)(3)</font></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Proposed maximum </font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">aggregate offering </font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">price (3)</font></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Amount of </font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">registration fee</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(2)(3)</font></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Common Stock,</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">$.01 par value</font></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block">&#160;</div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">250,000</font></div>
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<DIV STYLE="text-align: center; display: block">$1.17</div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center">$292,500</div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center">$37.68</div>
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<td valign="top" width="20%" style="BORDER-BOTTOM: black 2px solid; BORDER-LEFT: black 2px solid; BORDER-RIGHT: black 2px solid"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td valign="top" width="20%" style="BORDER-BOTTOM: black 2px solid"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td valign="top" width="20%" style="BORDER-BOTTOM: black 2px solid; BORDER-LEFT: black 2px solid; BORDER-RIGHT: black 2px solid"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td valign="top" width="20%" style="BORDER-BOTTOM: black 2px solid; BORDER-RIGHT: black 2px solid"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<div>
<table align="center" border="0" cellpadding="0" cellspacing="0"  width="100%" style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-SIZE: 10pt; FONT-FAMILY: times new roman">
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(1)</font></div>
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<td style="TEXT-ALIGN: left">
<div style="TEXT-ALIGN: left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">This registration statement covers 250,000 shares of common stock of the registrant, $0.01 par value (&#8220;Common Stock&#8221;), for issuance in connection with the ArQule, Inc. Amended and Restated 1996 Director Stock Option Plan (the &#8220;Plan&#8221;). Pursuant to Rule 416, promulgated under the Securities Act of 1933, as amended, an additional undeterminable number of shares of Common Stock is being registered to cover any adjustment in the number of shares of Common Stock issuable pursuant to the anti-dilution provisions of the Plan.</font></div>
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<div>
<table align="center" border="0" cellpadding="0" cellspacing="0"  width="100%" style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-SIZE: 10pt; FONT-FAMILY: times new roman">
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(2)</font></div>
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<td style="TEXT-ALIGN: left">
<div style="TEXT-ALIGN: left"><FONT STYLE="font: 10pt times new roman">Calculated on the basis of the average of the high and
low sale prices of the registrant&#8217;s Common Stock as reported on September 19, 2014 on the Nasdaq Global Market,which
date is within 5 business days prior to the date of the filing of this Registration Statement.</FONT></div>
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<div>
<table align="center" border="0" cellpadding="0" cellspacing="0"  width="100%" style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-SIZE: 10pt; FONT-FAMILY: times new roman">
<tr valign="top">
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(3)</font></div>
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<td style="TEXT-ALIGN: left">
<div style="TEXT-ALIGN: left"><FONT STYLE="font: 10pt times new roman">Estimated solely for the purpose of determining the registration
fee in accordance with Rule 457(h).</FONT></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">EXPLANATORY NOTE</font></div>

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<div style="TEXT-INDENT: 36pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">This Registration Statement on Form&#160;S-8 is being filed by ArQule, Inc., a Delaware corporation (the &#8220;Company&#8221;), and relates to the registration of 250,000 additional shares of the Company&#8217;s common stock, $.01 par value per share (the &#8220;Common Stock&#8221;) relating to ArQule, Inc.&#8217;s Amended and Restated 1996 Director Stock Option Plan (the &#8220;Plan&#8221;). The Company previously registered additional shares of Common Stock issuable under the Plan by Registration Statement No. 333-178228 on Form S-8 filed with the Securities and Exchange Commission (the &#8220;SEC&#8221;) on November 30, 2011.&#160;&#160;In accordance with General Instruction E to Form S-8, the contents of previously filed Registration Statements relating to the Plan are incorporated by reference herein to the extent not modified or superseded hereby or thereby or by a subsequently filed document.</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">PART I</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="FONT-SIZE: 10pt">&#160;</font></div>

<div style="TEXT-INDENT: 36pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">The document(s) containing the information specified in Part I will be sent or given to employees as specified by Rule 428(b)(1) of the Securities Act of 1933, as amended (the &#8220;Securities Act&#8221;). Such documents are not being filed with the SEC either as part of this Registration Statement or as prospectuses or prospectus supplements pursuant to Rule 424 of the Securities Act. Such documents and the documents incorporated by reference in this Registration Statement pursuant to Item 3 of Part II hereof, taken together, constitute a prospectus that meets the requirements of Section 10(a) of the Securities Act.</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">PART II</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">INFORMATION REQUIRED IN THE REGISTRATION STATEMENT</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">Item 3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="DISPLAY: inline; FONT-SIZE: 10pt; TEXT-DECORATION: underline">Incorporation of Documents by Reference</font>.</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font  style="MARGIN-LEFT: 36pt; FONT-SIZE: 10pt"></font><font style="FONT-SIZE: 10pt">The following documents filed by the Company<font style="DISPLAY: inline; FONT-SIZE: 10pt">&#160;</font><font style="DISPLAY: inline; FONT-SIZE: 10pt">(File No. 000-21429)</font><font style="DISPLAY: inline; FONT-SIZE: 10pt">&#160;w</font>ith the SEC under the Securities and Exchange Act of 1934, as amended (the &#8220;Exchange Act&#8221;) are incorporated herein by reference:</font></font></div>

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<div style="TEXT-INDENT: 18pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Annual Report on Form 10-K for the year ended December 31, 2013 filed with the SEC on March 5, 2014.</font></div>

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<div style="TEXT-INDENT: 18pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">2.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Quarterly Reports on Form 10-Q for the quarters ended March 31, 2014 (filed with the SEC on May&#160;7, 2014) and June 30, 2014 (filed with the SEC on August 5, 2014).</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="justify">&#160;</div>

<div style="TEXT-INDENT: 18pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Current Reports on Form 8-K filed with the SEC on January 16, 2014; January 27, 2014; February 4, 2014; May 16, 2014; and May 30, 2014.</font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="justify">&#160;</div>

<div style="TEXT-INDENT: 18pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">4.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The description of the Company&#8217;s Common Stock contained in the Registration Statement on Form&#160;8-A filed with the SEC on September 25, 1996, including any amendment or report filed for the purpose of updating such description.</font></div>

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<div style="TEXT-INDENT: 36pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">All documents filed by the Company after the date of this Registration Statement pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act, prior to the filing of a post-effective amendment which indicates that all Common Stock offered hereby has been sold or which deregisters such Common Stock then remaining unsold, shall be deemed to be incorporated in this Registration Statement by reference and shall be a part hereof from the date of filing of such documents.</font></div>

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<div style="TEXT-INDENT: 36pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Any statement contained in a document incorporated or deemed to be incorporated by reference in this Registration Statement shall be deemed to be modified or superseded for purposes of this Registration Statement to the extent that a statement contained herein or in any other subsequently filed document which also is or is deemed to be incorporated by reference in this Registration Statement modifies or supersedes such statement.&#160;&#160;Any such statement so modified or superseded shall not be deemed, except as so modified or so superseded, to constitute a part of this Registration Statement.</font></div>

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<td style="WIDTH: 72pt"><font style="DISPLAY: inline; FONT-WEIGHT: bold">Item 8.</font></td>
<td><font style="DISPLAY: inline; FONT-WEIGHT: bold"><font style="TEXT-DECORATION: underline">Exhibits</font></font></td>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Exhibit 4</font></div>
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<td>
<div align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">ArQule, Inc. Amended and Restated 1996 Director Stock Option Plan, as amended (incorporated by reference from Appendix C to the Company&#8217;s Definitive Proxy Statement on Schedule 14A for the 2014 Annual Meeting of Stockholders, as filed with the SEC on April 11,&#160;2014).</font></div>
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<td style="WIDTH: 72pt">Exhibit 5</td>
<td>Opinion of Robert J. Connaughton, Jr., filed herewith.</td>
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</div>

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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Exhibit 23.1</font></div>
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<div align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Consent of Robert J. Connaughton, Jr., included in the opinion filed as Exhibit 5 hereto.</font></div>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Exhibit 23.2</font></div>
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<td>
<div align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm, filed herewith.</font></div>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Exhibit 24</font></div>
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<td>
<div align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Powers of Attorney of certain officers and directors of ArQule, Inc. (included on the signature page to this Registration Statement).</font></div>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: -3.6pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">SIGNATURES</font></div>

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<div style="TEXT-INDENT: 36pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: -3.6pt" align="left"><FONT STYLE="font: 10pt times new roman">Pursuant
to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it
meets all of the requirements for filing on Form S-8 and has duly caused this registration statement to be signed on its behalf
by the undersigned, thereunto duly authorized, in the City of Woburn, Commonwealth of Massachusetts, on September 22,
2014.</FONT></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="justify">
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<TD STYLE="vertical-align: top"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="vertical-align: top"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
</tr><tr>
<TD STYLE="vertical-align: top; width: 50%"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD STYLE="vertical-align: top; width: 2%"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD STYLE="vertical-align: top; width: 30%"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD STYLE="vertical-align: top; width: 18%"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="text-align: left; vertical-align: top; border-bottom-color: #ffffff; border-bottom-style: solid">
<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></div>
</td>
<TD STYLE="vertical-align: top; border-bottom-color: #ffffff; border-bottom-style: solid">
<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">By:&#160;&#160; </font></div>
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<TD NOWRAP STYLE="text-align: left; vertical-align: top; border-bottom: black 2px solid"><FONT STYLE="font: 10pt times new roman">&#160;/s/
Paolo Pucci<FONT STYLE="letter-spacing: 3pt">&#160;</FONT></FONT></td>
<TD STYLE="vertical-align: top; border-bottom-color: #ffffff; border-bottom-style: solid"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="vertical-align: top"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD COLSPAN="2" STYLE="vertical-align: top"><FONT STYLE="font: 10pt times new roman">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Paolo
Pucci</FONT></td>
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<TD STYLE="vertical-align: top"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD COLSPAN="2" STYLE="vertical-align: top"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Chief Executive Officer</font></td>
<TD STYLE="vertical-align: top"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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</div>
</div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="justify">&#160;</div>

<div style="TEXT-INDENT: 36pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: -3.6pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Pursuant to the requirements of the Securities Act of 1933, this registration statement has been signed by the following persons in the capacities and on the dates indicated.</font></div>

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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-SIZE: 10pt; FONT-WEIGHT: bold">POWER OF ATTORNEY</font></font></div>

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<div style="TEXT-INDENT: 36pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">KNOW ALL PERSONS BY THESE PRESENTS that each person whose signature appears below constitutes and appoints, jointly and severally, Peter&#160;&#160;S. Lawrence and Robert J. Connaughton, Jr., his or her true and lawful attorney-in-fact and agents, each with full power of substitution, for him or her and in his or her name, place and stead, in any and all capacities, to sign any and all amendments, including post-effective amendments, to this registration statement, and to file the same, with all exhibits thereto and all other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as he or she&#160;&#160;might or could do in person, hereby ratifying and confirming all that each of said attorneys-in-fact and agents or either of them, or his or their substitute or substitutes, may lawfully do or cause to be done or by virtue thereof.</font></div>

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<div style="TEXT-INDENT: 36pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration Statement has been signed by the following persons in the capacities and on the dates indicated:</font></div>

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<DIV STYLE="text-align: center"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">TITLE:</font></font></div>
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<DIV STYLE="text-align: center"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">DATE:</font></font></div>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-SIZE: 10pt">/s/ Paolo Pucci&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font></font><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-SIZE: 10pt">&#160;</font></font></font></div>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Chief Executive Officer and Director</font></font></div>
</td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<DIV STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></div>
</td>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Paolo Pucci</font></font></div>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%">

<div align="left"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(Principal Executive Officer)</font></font></div>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
</tr><tr>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-SIZE: 10pt">/s/ Peter S. Lawrence</font></font></font></div>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td nowrap width="20%">

<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">President and Chief Operating Officer</font></font></div>
</td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD WIDTH="20%" STYLE="text-align: center">

<DIV STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></div>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Peter S. Lawrence</font></font></div>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%">

<div align="left"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(Principal Financial Officer)</font></font></div>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-SIZE: 10pt">/s/ Robert J. Weiskopf</font></font></font></div>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD NOWRAP STYLE="width: 20%">

<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Vice
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%" style="TEXT-ALIGN: left">

<DIV STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></div>
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<div style="TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Robert J. Weiskopf</font></font></div>
</td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD NOWRAP STYLE="width: 20%">

<div align="left"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">(Principal Accounting Officer)</font></font></div>
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<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td width="20%"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<div style="TEXT-ALIGN: left; TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt">&#160;</div>

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<div style="TEXT-ALIGN: center; TEXT-INDENT: 0pt; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">SIGNATURE:</font></font></div>
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<td width="20%">&#160;</td>
<td width="20%" style="TEXT-ALIGN: left">

<DIV STYLE="text-align: center"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">TITLE:</font></font></div>
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<DIV STYLE="text-align: center"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold">DATE:</font></font></div>
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<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="border-bottom: black 2px solid"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">/s/ Timothy C. Barabe</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Director</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></td>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Timothy C. Barabe</font></font></div>
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<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="border-bottom: black 2px solid"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">/s/ Susan L. Kelley</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Director</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></td>
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<TD>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Susan L. Kelley</font></font></div>
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<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
</tr><tr>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="border-bottom: black 2px solid"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">/s/ Ronald M. Lindsay&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Director</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></td>
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<TD>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Ronald M. Lindsay</font></font></div>
</td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
</tr><tr>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="border-bottom: black 2px solid"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">/s/ Michael D. Loberg&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Director</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></td>
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<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Michael D. Loberg</font></font></div>
</td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="border-bottom: black 2px solid"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">/s/ William G. Messenger</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">Director</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></td>
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<TD>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="left"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">William G. Messenger</font></font></div>
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<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
</tr><tr>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="border-bottom: black 2px solid"><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">/s/ Patrick J. Zenner</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<TD STYLE="text-align: center"><FONT STYLE="font: 10pt times new roman">September 22, 2014</FONT></td>
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<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<TD><font style="FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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<div>&#160;</div>

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<div>&#160;</div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block; MARGIN-LEFT: 0pt; MARGIN-RIGHT: 0pt" align="center"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt; FONT-WEIGHT: bold"><font style="DISPLAY: inline; FONT-SIZE: 10pt; TEXT-DECORATION: underline">INDEX TO EXHIBITS</font></font></div>

<div style="TEXT-INDENT: 0pt; DISPLAY: block">&#160;</div>

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<td valign="top" width="8%"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160; </font></td>
<td valign="top" width="2%"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
<td valign="top" width="90%"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160; </font></td>
</tr><tr>
<td align="left" nowrap valign="top" width="8%">
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<td valign="top" width="2%"><font style="DISPLAY: inline; FONT-FAMILY: times new roman; FONT-SIZE: 10pt">&#160;</font></td>
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[{"type": "S-8", "sequence": "1", "filename": "t80088_s8.htm", "description": "FORM S-8", "secsgml_size_bytes": 69695}]
{"company-data": {"conformed-name": "ARQULE INC", "cik": "0001019695", "assigned-sic": "2834", "irs-number": "043221586", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-198883", "film-number": "141114825"}, "business-address": {"street1": "19 PRESIDENTIAL WAY", "city": "WOBURN", "state": "MA", "zip": "01801", "phone": "781-994-0300"}, "mail-address": {"street1": "19 PRESIDENTIAL WAY", "city": "WOBURN", "state": "MA", "zip": "01801"}}
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C.  20549
FORM S-8
REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933
ARQULE, INC.
(Exact Name of registrant as specified in its charter)
Delaware
58-1959440
(State or other jurisdiction of
incorporation or organization)
(I.R.S. Employer
Identification No.)
19 Presidential Way,
Woburn, Massachusetts 01801
(Address, including zip code, of principal executive offices)
ArQule, Inc. Amended and Restated 1996 Director Stock Option Plan
(Full title of the plan)
Paolo Pucci
Chief Executive Officer
ArQule, Inc.
19 Presidential Way,
Woburn, Massachusetts 01801
(781) 994-0300
(Name, address, including zip code, and telephone number including area code, of agent for service)
Copy to:
Richard E. Baltz, Esq.
Arnold & Porter LLP
555 12
th
Street, N.W.
Washington, D.C.  20004
(202) 942-5000
Calculation of Registration Fee
Title of securities to be
registered
Amount to be
registered (1)
Proposed
maximum offering
price per unit (2)(3)
Proposed maximum
aggregate offering
price (3)
Amount of
registration fee
(2)(3)
Common Stock,
$.01 par value
250,000
$1.17
$292,500
$37.68
(1)
This registration statement covers 250,000 shares of common stock of the registrant, $0.01 par value ("Common Stock"), for issuance in connection with the ArQule, Inc. Amended and Restated 1996 Director Stock Option Plan (the "Plan"). Pursuant to Rule 416, promulgated under the Securities Act of 1933, as amended, an additional undeterminable number of shares of Common Stock is being registered to cover any adjustment in the number of shares of Common Stock issuable pursuant to the anti-dilution provisions of the Plan.
(2)
Calculated on the basis of the average of the high and
low sale prices of the registrant's Common Stock as reported on September 19, 2014 on the Nasdaq Global Market,which
date is within 5 business days prior to the date of the filing of this Registration Statement.
(3)
Estimated solely for the purpose of determining the registration
fee in accordance with Rule 457(h).
EXPLANATORY NOTE
This Registration Statement on Form S-8 is being filed by ArQule, Inc., a Delaware corporation (the "Company"), and relates to the registration of 250,000 additional shares of the Company's common stock, $.01 par value per share (the "Common Stock") relating to ArQule, Inc.'s Amended and Restated 1996 Director Stock Option Plan (the "Plan"). The Company previously registered additional shares of Common Stock issuable under the Plan by Registration Statement No. 333-178228 on Form S-8 filed with the Securities and Exchange Commission (the "SEC") on November 30, 2011.  In accordance with General Instruction E to Form S-8, the contents of previously filed Registration Statements relating to the Plan are incorporated by reference herein to the extent not modified or superseded hereby or thereby or by a subsequently filed document.
PART I
INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS
The document(s) containing the information specified in Part I will be sent or given to employees as specified by Rule 428(b)(1) of the Securities Act of 1933, as amended (the "Securities Act"). Such documents are not being filed with the SEC either as part of this Registration Statement or as prospectuses or prospectus supplements pursuant to Rule 424 of the Securities Act. Such documents and the documents incorporated by reference in this Registration Statement pursuant to Item 3 of Part II hereof, taken together, constitute a prospectus that meets the requirements of Section 10(a) of the Securities Act.
PART II
INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
Item 3.
Incorporation of Documents by Reference
.
The following documents filed by the Company
(File No. 000-21429)
w
ith the SEC under the Securities and Exchange Act of 1934, as amended (the "Exchange Act") are incorporated herein by reference:
1.         Annual Report on Form 10-K for the year ended December 31, 2013 filed with the SEC on March 5, 2014.
2.         Quarterly Reports on Form 10-Q for the quarters ended March 31, 2014 (filed with the SEC on May 7, 2014) and June 30, 2014 (filed with the SEC on August 5, 2014).
3.         Current Reports on Form 8-K filed with the SEC on January 16, 2014; January 27, 2014; February 4, 2014; May 16, 2014; and May 30, 2014.
4.         The description of the Company's Common Stock contained in the Registration Statement on Form 8-A filed with the SEC on September 25, 1996, including any amendment or report filed for the purpose of updating such description.
All documents filed by the Company after the date of this Registration Statement pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act, prior to the filing of a post-effective amendment which indicates that all Common Stock offered hereby has been sold or which deregisters such Common Stock then remaining unsold, shall be deemed to be incorporated in this Registration Statement by reference and shall be a part hereof from the date of filing of such documents.
Any statement contained in a document incorporated or deemed to be incorporated by reference in this Registration Statement shall be deemed to be modified or superseded for purposes of this Registration Statement to the extent that a statement contained herein or in any other subsequently filed document which also is or is deemed to be incorporated by reference in this Registration Statement modifies or supersedes such statement.  Any such statement so modified or superseded shall not be deemed, except as so modified or so superseded, to constitute a part of this Registration Statement.
Item 8.
Exhibits
Exhibit 4
ArQule, Inc. Amended and Restated 1996 Director Stock Option Plan, as amended (incorporated by reference from Appendix C to the Company's Definitive Proxy Statement on Schedule 14A for the 2014 Annual Meeting of Stockholders, as filed with the SEC on April 11, 2014).
Exhibit 5
Opinion of Robert J. Connaughton, Jr., filed herewith.
Exhibit 23.1
Consent of Robert J. Connaughton, Jr., included in the opinion filed as Exhibit 5 hereto.
Exhibit 23.2
Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm, filed herewith.
Exhibit 24
Powers of Attorney of certain officers and directors of ArQule, Inc. (included on the signature page to this Registration Statement).
SIGNATURES
Pursuant
to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it
meets all of the requirements for filing on Form S-8 and has duly caused this registration statement to be signed on its behalf
by the undersigned, thereunto duly authorized, in the City of Woburn, Commonwealth of Massachusetts, on September 22,
2014.
ARQULE, INC.
By:
/s/
Paolo Pucci
Paolo
Pucci
Chief Executive Officer
Pursuant to the requirements of the Securities Act of 1933, this registration statement has been signed by the following persons in the capacities and on the dates indicated.
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS that each person whose signature appears below constitutes and appoints, jointly and severally, Peter  S. Lawrence and Robert J. Connaughton, Jr., his or her true and lawful attorney-in-fact and agents, each with full power of substitution, for him or her and in his or her name, place and stead, in any and all capacities, to sign any and all amendments, including post-effective amendments, to this registration statement, and to file the same, with all exhibits thereto and all other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as he or she  might or could do in person, hereby ratifying and confirming all that each of said attorneys-in-fact and agents or either of them, or his or their substitute or substitutes, may lawfully do or cause to be done or by virtue thereof.
Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration Statement has been signed by the following persons in the capacities and on the dates indicated:
SIGNATURE:
TITLE:
DATE:
/s/ Paolo Pucci
Chief Executive Officer and Director
September 22, 2014
Paolo Pucci
(Principal Executive Officer)
/s/ Peter S. Lawrence
President and Chief Operating Officer
September 22, 2014
Peter S. Lawrence
(Principal Financial Officer)
/s/ Robert J. Weiskopf
Vice
President, Finance, Controller & Treasurer
September 22, 2014
Robert J. Weiskopf
(Principal Accounting Officer)
SIGNATURE:
TITLE:
DATE:
/s/ Timothy C. Barabe
Director
September 22, 2014
Timothy C. Barabe
/s/ Susan L. Kelley
Director
September 22, 2014
Susan L. Kelley
/s/ Ronald M. Lindsay
Director
September 22, 2014
Ronald M. Lindsay
/s/ Michael D. Loberg
Director
September 22, 2014
Michael D. Loberg
/s/ William G. Messenger
Director
September 22, 2014
William G. Messenger
/s/ Patrick J. Zenner
Director, Chairman of the Board
September 22, 2014
Patrick J. Zenner
INDEX TO EXHIBITS
Exhibit 4
ArQule, Inc. Amended and Restated 1996 Director Stock Option Plan (incorporated by reference from Appendix C to the Company's Definitive Proxy Statement on Schedule 14A for the 2014 Annual Meeting of Stockholders, as filed with the SEC on April 11, 2014).
Exhibit 5
Opinion of Robert J. Connaughton, Jr., filed herewith.
Exhibit 23.1
Consent of Robert J. Connaughton, Jr., included in the opinion filed as Exhibit 5 hereto.
Exhibit 23.2
Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm, filed herewith.
Exhibit 24
Powers of Attorney of certain officers and directors of ArQule, Inc. (included on the signature page to this Registration Statement).