SECURITIES AND EXCHANGE COMMISSION

FORM S-8

REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933

ARQULE, INC.

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)

Dr. Stephen A. Hill
President and 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
555 12^th Street, N.W.
Washington, D.C. 20004
(202) 942-5124

Calculation of Registration Fee

The prospectus which will be part of this registration statement is a combined prospectus under SEC Rule 429 intended to be used for the offering of (a) the shares of the Company’s Common Stock registered hereunder, and (b) the shares of the Company’s Common Stock remaining to be issued which have been previously registered by Registration Statements on Form S-8 File Nos. 333-25369, 333-43046, and 333-105297.

Table of Contents

EXPLANATORY NOTE AND INCORPORATION BY REFERENCE

     This Registration Statement registers additional securities of the same class as other securities for which a registration statement filed on Form S-8 relating to the ArQule, Inc. (the “Company”) Amended and Restated 1996 Director Stock Option Plan (the “Plan”) is already effective. In accordance with General Instruction E to Form S-8, the contents of (i) the Company’s Registration Statement on Form S-8 (File No. 333-25369) filed with the Securities Exchange Commission (the “Commission”) on April 17, 1997, relating to the registration of 125,000 shares of the Company’s common stock, $.01 par value per share (the “Common Stock”) authorized for issuance under the Plan, (ii) the Company’s Registration Statement on Form S-8 (File No. 333-43046) filed with the Commission on August 4, 2000, relating to the registration of 65,500 shares of Common Stock authorized for issuance under the Plan, and (iii) the Company’s Registration Statement on Form S-8 (File No. 333-105297) filed with the Commission on May 15, 2003, relating to the registration of 100,000 shares of Common Stock authorized for issuance under the Plan are incorporated by reference in their entirety in this Registration Statement.

     This Registration Statement provides for the registration of an additional 60,000 shares of Common Stock authorized for issuance under the Plan.

PART II

Item 3.      Incorporation of Documents by Reference.

     The following documents filed by the Company (File No. 000-20713) with the Commission under the Securities Exchange Act of 1934, as amended (“Exchange Act”), are incorporated herein by reference:

     All documents filed by the Registrant 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

SIGNATURES

     Pursuant to the requirements of the Securities Act of 1933, as amended, the Company 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, State of Massachusetts, on March 16, 2005.

     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:

INDEX TO EXHIBITS