content: <PAGE>   1
       As filed with the Securities and Exchange Commission on January 9, 1997
  
                                                             REGISTRATION NO. 333-
  ================================================================================
  
                         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                                04-3221586
       (State or other jurisdiction           (I.R.S. Employer Identification No.)
               of incorporation)
  
      200 BOSTON AVENUE, MEDFORD, MASSACHUSETTS              02155
       (Address of Principal Executive Offices)           (Zip Code)
  
  
                             ---------------------------
  
                          1996 EMPLOYEE STOCK PURCHASE PLAN
                              (Full Title of the Plan)
  
                                   ERIC B. GORDON
                        PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                    ArQule, Inc.
                                  200 Boston Avenue
                                  Medford, MA 02155
                       (Name and Address of Agent For Service)
  
                                   (617) 395-4100
                       (Telephone Number, Including Area Code
                                of Agent For Service)
  
                             ---------------------------
  
  
  
  <TABLE>
  
                                               CALCULATION OF REGISTRATION FEE
  -----------------------------------------------------------------------------------------------------------------------
  <CAPTION>
      Title Of Securities To Be        Amount To Be          Proposed            Proposed Maximum       Amount Of
              Registered                Registered       Maximum Offering       Aggregate Offering   Registration Fee
                                                        Price Per Share(1)           Price(1)
  -----------------------------------------------------------------------------------------------------------------------
  <S>                                   <C>                   <C>                   <C>                  <C>
  Common Stock, $0.01 par value         120,000               $15.25                $1,830,000           $554.55
  -----------------------------------------------------------------------------------------------------------------------
  </TABLE>
  
  (1)  Estimated solely for the purpose of determining the registration fee and
       computed pursuant to Rule 457(h) based upon the average of the high and low
       sale prices on January 2, 1997 as reported by the Nasdaq National Market.
  ================================================================================
  
                                    Page 1 of 10
                           Exhibit Index appears at Page 8
  
  
  <PAGE>   2
  
  
                                       PART I
                INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS
  
       The information required by Part I is included in the documents sent or
  given to participants in the 1996 Employee Stock Purchase Plan of ArQule, Inc.
  (the "Registrant") pursuant to Rule 428(b)(1) of the Securities Act of 1933, as
  amended (the "Securities Act").
  
                                       PART II
                 INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
  
  Item 3. Incorporation of Documents by Reference.
  -----------------------------------------------
  
       The Registrant is subject to the informational and reporting requirements
  of Sections 13(a), 14 and 15(d) of the Securities Exchange Act of 1934, as
  amended (the "Exchange Act"), and in accordance therewith files reports, proxy
  statements and other information with the Securities and Exchange Commission
  (the "Commission"). The following documents filed with the Commission are
  incorporated herein by reference:
  
       (a) The Registrant's latest annual report filed pursuant to Section 13(a)
  or 15(d) of the Exchange Act, or the latest prospectus filed pursuant to Rule
  424(b), or otherwise, under the Securities Act that contains, either directly or
  by incorporation by reference, audited financial statements for the Registrant's
  latest fiscal year for which such statements have been filed.
  
       (b) All reports filed by the Registrant pursuant to Section 13(a) or 15(d)
  of the Exchange Act since the end of the fiscal year covered by the annual
  report or prospectus referred to in (a) above.
  
       (c) The description of the common stock of the Registrant, par value $.01
  per share (the "Common Stock"), contained in a registration statement filed
  under the Exchange Act, including any amendment or report filed for the purpose
  of updating such description.
  
       (d) The Registrant's definitive proxy statement or information statement,
  if any, filed pursuant to Section 14 of the Exchange Act in connection with the
  latest annual meeting of its stockholders, and any definitive proxy or
  information statements so filed in connection with any subsequent special
  meetings of its stockholders.
  
       (e) Information as to stock options, including the amount outstanding,
  exercises, prices and expiration dates, included in the Registrant's definitive
  proxy statement, described in (d) above and which will be included in the future
  either in the Registrant's proxy statements, annual reports or appendices to the
  prospectus.
  
       All documents filed after the date of this Registration Statement by the
  Registrant pursuant to Section 13(a), 13(d), 14 and 15(d) of the Exchange Act
  and prior to the filing of a post-effective amendment that indicates that all
  shares of Common Stock offered hereunder have been sold or which deregisters all
  shares of Common Stock remaining unsold shall be deemed to be incorporated by
  reference herein and to be a part hereof from the date of the filing of such
  reports and documents.
  
  Item 4. Description of Securities.
  ---------------------------------
  
       Not Applicable.
  
                                    Page 2 of 10
  
  
  <PAGE>   3
  
  
  
  
  Item 5. Interests of Named Experts and Counsel.
  ----------------------------------------------
  
       Not Applicable.
  
  Item 6. Indemnification of Directors and Officers.
  -------------------------------------------------
  
       Section 145 of the Delaware General Corporation Law permits the Registrant
  to indemnify directors, officers, employees and agents of the Registrant against
  actual and reasonable expenses (including attorneys' fees) incurred by them in
  connection with any action, suit or proceeding brought against them by reason of
  their status or service as a director, officer, employee or agent by or on
  behalf of the Registrant, and against expenses (including attorneys' fees),
  judgments, fines and settlements actually and reasonably incurred by him in
  connection with any such action, suit or proceeding, if (i) he acted in good
  faith and in a manner he reasonably believed to be in or not opposed to the best
  interests of the Registrant, and (ii) in the case of a criminal proceeding, he
  had no reasonable cause to believe his conduct was unlawful. Except as ordered
  by a court, no indemnification shall be made in connection with any proceeding
  brought by or in the right of the corporation where the person involved is
  adjudged to be liable to the Registrant.
  
       Article FIFTH of the Registrant's Amended and Restated Certificate of
  Incorporation provides that a director shall not be personally liable to the
  Registrant or its stockholders for monetary damages for breach of fiduciary duty
  as a director, except to the extent that elimination or limitation of liability
  is not permitted under the Delaware General Corporation Law as in effect when
  such liability is determined.
  
       Article V of the Registrant's Amended and Restated By-Laws provide that the
  Registrant shall, to the fullest extent permitted by the General Corporation Law
  of the State of Delaware, as amended from time to time, indemnify each person
  who was or is a party or is threatened to be made a party to any threatened,
  pending or completed action, suit or proceeding whether civil, criminal,
  administrative or investigative, by reason of the fact that he is or was, or has
  agreed to become a director or officer of the Registrant, or is or was serving,
  or has agreed to serve at the request of the Registrant as a director, officer
  or trustee of, or in a similar capacity with, another corporation, partnership,
  joint venture, trust or other enterprise. The indemnification provided for in
  Article V is expressly not exclusive of any other rights to which those seeking
  indemnification may be entitled under any law, agreement or vote of stockholders
  or disinterested directors or otherwise, and shall inure to the benefit of the
  heirs, executors and administrators of such persons. Article V further permits
  the Board of Directors to authorize the grant of indemnification rights to other
  employees and agents of the Registrant and such rights may be equivalent to, or
  greater or less than, those set forth in Article V.
  
       Article V of the Registrant's Amended and Restated By-Laws also provides
  that the Registrant shall have the power to purchase and maintain insurance on
  behalf of any person who is or was a director, officer, employee or agent of the
  Registrant, or is or was serving at the request of the Registrant as a director,
  officer, employee or agent of another corporation, partnership, joint venture,
  trust or other enterprise against any liability asserted against such person and
  incurred by such person in any such capacity or arising out of such person's
  status as such. The Registrant maintains insurance for directors and officers.
  
       Article V of the Registrant's Amended and Restated By-Laws provides that
  the Registrant shall indemnify any and all of its directors or officers, who
  serve as an officer or director of the Registrant
  
                                    Page 3 of 10
  
  
  <PAGE>   4
  
  
  
  or of any other corporation at the request of the Registrant, to the fullest
  extent permitted under and in accordance with the laws of the state of Delaware.
  
  Item 7. Exemption from Registration Claimed.
  -------------------------------------------
  
       Not Applicable.
  
  Item 8. Exhibits.
  ----------------
  
       The Exhibit Index immediately preceding the exhibits is incorporated herein
  by reference.
  
  Item 9. Undertakings.
  --------------------
  
       (a) The undersigned Registrant hereby undertakes:
  
            (1) To file, during any period in which offers or sales are being
  made, a post-effective amendment to this registration statement:
  
                 (i) To include any prospectus required by Section 10(a)(3) of the
  Securities Act of 1933;
  
                 (ii) To reflect in the prospectus any facts or events arising
  after the effective date of this Registration Statement (or the most recent
  post-effective amendment thereof) which, individually or in the aggregate,
  represents a fundamental change in the information set forth in this
  Registration Statement;
  
                 (iii) To include any material information with respect to the
  plan of distribution not previously disclosed in this Registration Statement or
  any material change to such information in this Registration Statement;
  
  
  PROVIDED, HOWEVER, that paragraphs (a)(1)(i) and (a)(1)(ii) do not apply if the
  information required to be included in a post-effective amendment by those
  paragraphs is contained in periodic reports filed by the Registrant pursuant to
  Section 13 or Section 15(d) of the Securities Exchange Act of 1934 that are
  incorporated by reference in this Registration Statement.
  
            (2) That, for the purpose of determining any liability under the
  Securities Act of 1933, each such post-effective amendment shall be deemed to be
  a new registration statement relating to the securities offered therein, and the
  offering of such securities at that time shall be deemed to be the initial bona
  fide offering thereof.
  
            (3) To remove from registration by means of a post-effective amendment
  any of the securities being registered which remain unsold at the termination of
  the offering.
  
       (b) The undersigned Registrant hereby undertakes that, for purposes of
  determining any liability under the Securities Act of 1933, each filing of the
  Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
  Securities Exchange Act of 1934 that is incorporated by reference in this
  Registration Statement shall be deemed to be a new registration statement
  relating to the securities offered
  
                                    Page 4 of 10
  
  
  <PAGE>   5
  
  
  
  therein, and the offering of such securities at that time shall be deemed to be
  the initial bona fide offering thereof.
  
       (c) Insofar as indemnification for liabilities arising under the Securities
  Act of 1933 may be permitted to directors, officers and controlling persons of
  the Registrant pursuant to the provisions referred to in Item 6 hereof, or
  otherwise, the Registrant has been advised that in the opinion of the Securities
  and Exchange Commission such indemnification is against public policy as
  expressed in the Act and is, therefore, unenforceable. In the event that a claim
  for indemnification against such liabilities (other than the payment by the
  Registrant of expenses incurred or paid by a director, officer or controlling
  person of the registrant in the successful defense of any action, suit or
  proceeding) is asserted by such director, officer or controlling person in
  connection with the securities being registered, the Registrant will, unless in
  the opinion of its counsel the matter has been settled by controlling precedent,
  submit to a court of appropriate jurisdiction the question whether such
  indemnification by it is against public policy as expressed in the Act and will
  be governed by the final adjudication of such issue.
  
                                    Page 5 of 10
  
  
  <PAGE>   6
  
  
  
  
                                     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 Medford, Massachusetts, on this 9th day of January,
  1997.
  
                                       ARQULE, INC.
  
                                       By:  /s/ Eric B. Gordon
                                          ----------------------------------------
                                            Eric B. Gordon
                                            President and Chief Executive Officer
  
                                    Page 6 of 10
  
  
  <PAGE>   7
  
  
  
  
                                  POWER OF ATTORNEY
  
       We, the undersigned officers and directors of ArQule, Inc. hereby severally
  constitute and appoint Eric B. Gordon, Michael Lytton and Lynnette C. Fallon,
  and each of them singly, our true and lawful attorneys-in-fact, with full power
  to them in any and all capacities, to sign any and all amendments to this
  Registration Statement on Form S-8 including any post-effective amendments
  thereto, and to file the same, with exhibits thereto and other documents in
  connection therewith, with the Securities and Exchange Commission, hereby
  ratifying and confirming all that each of said attorneys-in-fact may do or cause
  to be done by virtue hereof.
  
  <TABLE>
       Pursuant to the requirements of the Securities Act of 1933, this
  Registration Statement has been signed below by the following persons in the
  capacities and on the dates indicated:
  
  <CAPTION>
           SIGNATURE                      TITLE                               DATE
           ---------                      -----                               ----
                                                                         
  <S>                             <C>                                    <C>
  /s/ Eric B. Gordon              President, Chief Executive             January 9, 1997
  -----------------------------   Officer and Director                   
  Eric B. Gordon                  (Principal Executive                   
                                  Officer)                               
                                                                         
  /s/ James R. Fitzgerald         Vice President and Chief Financial     January 9, 1997
  -----------------------------   Officer (Principal Financial           
  James R. Fitzgerald             Officer and Principal Accounting       
                                  Officer)                               
                                                                         
  /s/ Stephen M. Dow              Director                               January 9, 1997
  -----------------------------                                                                     
  Stephen M. Dow                                                         
                                                                         
  /s/ Joseph C. Hogan, Jr.        Director, Chief Scientific             January 9, 1997
  -----------------------------   Officer                                                             
  Joseph C. Hogan, Jr.                                            
                                                                         
  /s/ Adrian de Jonge             Director                               January 9, 1997
  -----------------------------                                                                       
  Adrian de Jonge                                                        
                                                                         
  /s/ Allan R. Ferguson           Director                               January 9, 1997
  -----------------------------                                                                       
  Allan R. Ferguson                                                      
  </TABLE>
                                                                         
  
                                    Page 7 of 10
  
  
  <PAGE>   8
  
  
  <TABLE>
                                    EXHIBIT INDEX
                                    -------------
  <CAPTION>
  Exhibit Number                       Description                         Page Number
  --------------                       -----------                         -----------
  
  <S>              <C>                                                          <C>
       4.1         Amended and Restated Certificate of Incorporation of         (1)
                   the Registrant.
  
       4.2         Amended and Restated By-Laws of the Registrant.              (1)
  
  
       4.3         Specimen certificate for shares of Common Stock, $.01 
                   par value per share of the Registrant.                       (1)
  
       5.1         Opinion of Palmer & Dodge LLP as to the legality of
                   the securities registered hereunder.                          9
  
      23.1         Consent of Price Waterhouse LLP, independent                 10
                   accountants.
  
      23.2         Consent of Palmer & Dodge LLP (contained in
                   Opinion of Palmer & Dodge LLP, filed as Exhibit
                   5.1).
  
      24.1         Power of Attorney (set forth on the signature page to
                   this Registration Statement).
  
  <FN>
  -----------------------
  (1)  Filed as an exhibit to the Registrant's Registration Statement on Form S-1
       (File No. 333-11105) declared effective on October 16, 1996 and
       incorporated herein by reference.
  </TABLE>
  
                                    Page 8 of 10
metadata_documents: [{"type": "S-8", "sequence": "1", "description": "ARQULE, INC.", "secsgml_size_bytes": 20025}]
metadata_filer: {"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": "333-19469", "film-number": "97503294"}, "business-address": {"street1": "200 BOSTON AVE", "city": "MEDFORD", "state": "MA", "zip": "02155", "phone": "6173954100"}, "mail-address": {"street1": "200 BOSTON AVE", "city": "MEDFORD", "state": "MA", "zip": "02155"}}
text: 1
       As filed with the Securities and Exchange Commission on January 9, 1997
  
                                                             REGISTRATION NO. 333-
  ================================================================================
  
                         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                                04-3221586
       (State or other jurisdiction           (I.R.S. Employer Identification No.)
               of incorporation)
  
      200 BOSTON AVENUE, MEDFORD, MASSACHUSETTS              02155
       (Address of Principal Executive Offices)           (Zip Code)
  
                             ---------------------------
  
                          1996 EMPLOYEE STOCK PURCHASE PLAN
                              (Full Title of the Plan)
  
                                   ERIC B. GORDON
                        PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                    ArQule, Inc.
                                  200 Boston Avenue
                                  Medford, MA 02155
                       (Name and Address of Agent For Service)
  
                                   (617) 395-4100
                       (Telephone Number, Including Area Code
                                of Agent For Service)
  
                             ---------------------------
  
                                               CALCULATION OF REGISTRATION FEE
  -----------------------------------------------------------------------------------------------------------------------
  Title Of Securities To Be        Amount To Be          Proposed            Proposed Maximum       Amount Of
              Registered                Registered       Maximum Offering       Aggregate Offering   Registration Fee
                                                        Price Per Share(1)           Price(1)
  -----------------------------------------------------------------------------------------------------------------------
  Common Stock, $0.01 par value         120,000               $15.25                $1,830,000           $554.55
  -----------------------------------------------------------------------------------------------------------------------
  (1)  Estimated solely for the purpose of determining the registration fee and
       computed pursuant to Rule 457(h) based upon the average of the high and low
       sale prices on January 2, 1997 as reported by the Nasdaq National Market.
  ================================================================================
  
                                    Page 1 of 10
                           Exhibit Index appears at Page 8
  2
  
                                       PART I
                INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS
  
       The information required by Part I is included in the documents sent or
  given to participants in the 1996 Employee Stock Purchase Plan of ArQule, Inc.
  (the "Registrant") pursuant to Rule 428(b)(1) of the Securities Act of 1933, as
  amended (the "Securities Act").
  
                                       PART II
                 INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
  
  Item 3. Incorporation of Documents by Reference.
  -----------------------------------------------
  
       The Registrant is subject to the informational and reporting requirements
  of Sections 13(a), 14 and 15(d) of the Securities Exchange Act of 1934, as
  amended (the "Exchange Act"), and in accordance therewith files reports, proxy
  statements and other information with the Securities and Exchange Commission
  (the "Commission"). The following documents filed with the Commission are
  incorporated herein by reference:
  
       (a) The Registrant's latest annual report filed pursuant to Section 13(a)
  or 15(d) of the Exchange Act, or the latest prospectus filed pursuant to Rule
  424(b), or otherwise, under the Securities Act that contains, either directly or
  by incorporation by reference, audited financial statements for the Registrant's
  latest fiscal year for which such statements have been filed.
  
       (b) All reports filed by the Registrant pursuant to Section 13(a) or 15(d)
  of the Exchange Act since the end of the fiscal year covered by the annual
  report or prospectus referred to in (a) above.
  
       (c) The description of the common stock of the Registrant, par value $.01
  per share (the "Common Stock"), contained in a registration statement filed
  under the Exchange Act, including any amendment or report filed for the purpose
  of updating such description.
  
       (d) The Registrant's definitive proxy statement or information statement,
  if any, filed pursuant to Section 14 of the Exchange Act in connection with the
  latest annual meeting of its stockholders, and any definitive proxy or
  information statements so filed in connection with any subsequent special
  meetings of its stockholders.
  
       (e) Information as to stock options, including the amount outstanding,
  exercises, prices and expiration dates, included in the Registrant's definitive
  proxy statement, described in (d) above and which will be included in the future
  either in the Registrant's proxy statements, annual reports or appendices to the
  prospectus.
  
       All documents filed after the date of this Registration Statement by the
  Registrant pursuant to Section 13(a), 13(d), 14 and 15(d) of the Exchange Act
  and prior to the filing of a post-effective amendment that indicates that all
  shares of Common Stock offered hereunder have been sold or which deregisters all
  shares of Common Stock remaining unsold shall be deemed to be incorporated by
  reference herein and to be a part hereof from the date of the filing of such
  reports and documents.
  
  Item 4. Description of Securities.
  ---------------------------------
  
       Not Applicable.
  
                                    Page 2 of 10
  3
  
  Item 5. Interests of Named Experts and Counsel.
  ----------------------------------------------
  
       Not Applicable.
  
  Item 6. Indemnification of Directors and Officers.
  -------------------------------------------------
  
       Section 145 of the Delaware General Corporation Law permits the Registrant
  to indemnify directors, officers, employees and agents of the Registrant against
  actual and reasonable expenses (including attorneys' fees) incurred by them in
  connection with any action, suit or proceeding brought against them by reason of
  their status or service as a director, officer, employee or agent by or on
  behalf of the Registrant, and against expenses (including attorneys' fees),
  judgments, fines and settlements actually and reasonably incurred by him in
  connection with any such action, suit or proceeding, if (i) he acted in good
  faith and in a manner he reasonably believed to be in or not opposed to the best
  interests of the Registrant, and (ii) in the case of a criminal proceeding, he
  had no reasonable cause to believe his conduct was unlawful. Except as ordered
  by a court, no indemnification shall be made in connection with any proceeding
  brought by or in the right of the corporation where the person involved is
  adjudged to be liable to the Registrant.
  
       Article FIFTH of the Registrant's Amended and Restated Certificate of
  Incorporation provides that a director shall not be personally liable to the
  Registrant or its stockholders for monetary damages for breach of fiduciary duty
  as a director, except to the extent that elimination or limitation of liability
  is not permitted under the Delaware General Corporation Law as in effect when
  such liability is determined.
  
       Article V of the Registrant's Amended and Restated By-Laws provide that the
  Registrant shall, to the fullest extent permitted by the General Corporation Law
  of the State of Delaware, as amended from time to time, indemnify each person
  who was or is a party or is threatened to be made a party to any threatened,
  pending or completed action, suit or proceeding whether civil, criminal,
  administrative or investigative, by reason of the fact that he is or was, or has
  agreed to become a director or officer of the Registrant, or is or was serving,
  or has agreed to serve at the request of the Registrant as a director, officer
  or trustee of, or in a similar capacity with, another corporation, partnership,
  joint venture, trust or other enterprise. The indemnification provided for in
  Article V is expressly not exclusive of any other rights to which those seeking
  indemnification may be entitled under any law, agreement or vote of stockholders
  or disinterested directors or otherwise, and shall inure to the benefit of the
  heirs, executors and administrators of such persons. Article V further permits
  the Board of Directors to authorize the grant of indemnification rights to other
  employees and agents of the Registrant and such rights may be equivalent to, or
  greater or less than, those set forth in Article V.
  
       Article V of the Registrant's Amended and Restated By-Laws also provides
  that the Registrant shall have the power to purchase and maintain insurance on
  behalf of any person who is or was a director, officer, employee or agent of the
  Registrant, or is or was serving at the request of the Registrant as a director,
  officer, employee or agent of another corporation, partnership, joint venture,
  trust or other enterprise against any liability asserted against such person and
  incurred by such person in any such capacity or arising out of such person's
  status as such. The Registrant maintains insurance for directors and officers.
  
       Article V of the Registrant's Amended and Restated By-Laws provides that
  the Registrant shall indemnify any and all of its directors or officers, who
  serve as an officer or director of the Registrant
  
                                    Page 3 of 10
  4
  
  or of any other corporation at the request of the Registrant, to the fullest
  extent permitted under and in accordance with the laws of the state of Delaware.
  
  Item 7. Exemption from Registration Claimed.
  -------------------------------------------
  
       Not Applicable.
  
  Item 8. Exhibits.
  ----------------
  
       The Exhibit Index immediately preceding the exhibits is incorporated herein
  by reference.
  
  Item 9. Undertakings.
  --------------------
  
       (a) The undersigned Registrant hereby undertakes:
  
            (1) To file, during any period in which offers or sales are being
  made, a post-effective amendment to this registration statement:
  
                 (i) To include any prospectus required by Section 10(a)(3) of the
  Securities Act of 1933;
  
                 (ii) To reflect in the prospectus any facts or events arising
  after the effective date of this Registration Statement (or the most recent
  post-effective amendment thereof) which, individually or in the aggregate,
  represents a fundamental change in the information set forth in this
  Registration Statement;
  
                 (iii) To include any material information with respect to the
  plan of distribution not previously disclosed in this Registration Statement or
  any material change to such information in this Registration Statement;
  
  PROVIDED, HOWEVER, that paragraphs (a)(1)(i) and (a)(1)(ii) do not apply if the
  information required to be included in a post-effective amendment by those
  paragraphs is contained in periodic reports filed by the Registrant pursuant to
  Section 13 or Section 15(d) of the Securities Exchange Act of 1934 that are
  incorporated by reference in this Registration Statement.
  
            (2) That, for the purpose of determining any liability under the
  Securities Act of 1933, each such post-effective amendment shall be deemed to be
  a new registration statement relating to the securities offered therein, and the
  offering of such securities at that time shall be deemed to be the initial bona
  fide offering thereof.
  
            (3) To remove from registration by means of a post-effective amendment
  any of the securities being registered which remain unsold at the termination of
  the offering.
  
       (b) The undersigned Registrant hereby undertakes that, for purposes of
  determining any liability under the Securities Act of 1933, each filing of the
  Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
  Securities Exchange Act of 1934 that is incorporated by reference in this
  Registration Statement shall be deemed to be a new registration statement
  relating to the securities offered
  
                                    Page 4 of 10
  5
  
  therein, and the offering of such securities at that time shall be deemed to be
  the initial bona fide offering thereof.
  
       (c) Insofar as indemnification for liabilities arising under the Securities
  Act of 1933 may be permitted to directors, officers and controlling persons of
  the Registrant pursuant to the provisions referred to in Item 6 hereof, or
  otherwise, the Registrant has been advised that in the opinion of the Securities
  and Exchange Commission such indemnification is against public policy as
  expressed in the Act and is, therefore, unenforceable. In the event that a claim
  for indemnification against such liabilities (other than the payment by the
  Registrant of expenses incurred or paid by a director, officer or controlling
  person of the registrant in the successful defense of any action, suit or
  proceeding) is asserted by such director, officer or controlling person in
  connection with the securities being registered, the Registrant will, unless in
  the opinion of its counsel the matter has been settled by controlling precedent,
  submit to a court of appropriate jurisdiction the question whether such
  indemnification by it is against public policy as expressed in the Act and will
  be governed by the final adjudication of such issue.
  
                                    Page 5 of 10
  6
  
                                     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 Medford, Massachusetts, on this 9th day of January,
  1997.
  
                                       ARQULE, INC.
  
                                       By:  /s/ Eric B. Gordon
                                          ----------------------------------------
                                            Eric B. Gordon
                                            President and Chief Executive Officer
  
                                    Page 6 of 10
  7
  
                                  POWER OF ATTORNEY
  
       We, the undersigned officers and directors of ArQule, Inc. hereby severally
  constitute and appoint Eric B. Gordon, Michael Lytton and Lynnette C. Fallon,
  and each of them singly, our true and lawful attorneys-in-fact, with full power
  to them in any and all capacities, to sign any and all amendments to this
  Registration Statement on Form S-8 including any post-effective amendments
  thereto, and to file the same, with exhibits thereto and other documents in
  connection therewith, with the Securities and Exchange Commission, hereby
  ratifying and confirming all that each of said attorneys-in-fact may do or cause
  to be done by virtue hereof.
  
       Pursuant to the requirements of the Securities Act of 1933, this
  Registration Statement has been signed below by the following persons in the
  capacities and on the dates indicated:
  SIGNATURE                      TITLE                               DATE
           ---------                      -----                               ----
  /s/ Eric B. Gordon              President, Chief Executive             January 9, 1997
  -----------------------------   Officer and Director                   
  Eric B. Gordon                  (Principal Executive                   
                                  Officer)                               
                                                                         
  /s/ James R. Fitzgerald         Vice President and Chief Financial     January 9, 1997
  -----------------------------   Officer (Principal Financial           
  James R. Fitzgerald             Officer and Principal Accounting       
                                  Officer)                               
                                                                         
  /s/ Stephen M. Dow              Director                               January 9, 1997
  -----------------------------                                                                     
  Stephen M. Dow                                                         
                                                                         
  /s/ Joseph C. Hogan, Jr.        Director, Chief Scientific             January 9, 1997
  -----------------------------   Officer                                                             
  Joseph C. Hogan, Jr.                                            
                                                                         
  /s/ Adrian de Jonge             Director                               January 9, 1997
  -----------------------------                                                                       
  Adrian de Jonge                                                        
                                                                         
  /s/ Allan R. Ferguson           Director                               January 9, 1997
  -----------------------------                                                                       
  Allan R. Ferguson
  Page 7 of 10
  8
  
                                    EXHIBIT INDEX
                                    -------------
  Exhibit Number                       Description                         Page Number
  --------------                       -----------                         -----------
  4.1         Amended and Restated Certificate of Incorporation of         (1)
                   the Registrant.
  
       4.2         Amended and Restated By-Laws of the Registrant.              (1)
  
       4.3         Specimen certificate for shares of Common Stock, $.01 
                   par value per share of the Registrant.                       (1)
  
       5.1         Opinion of Palmer & Dodge LLP as to the legality of
                   the securities registered hereunder.                          9
  
      23.1         Consent of Price Waterhouse LLP, independent                 10
                   accountants.
  
      23.2         Consent of Palmer & Dodge LLP (contained in
                   Opinion of Palmer & Dodge LLP, filed as Exhibit
                   5.1).
  
      24.1         Power of Attorney (set forth on the signature page to
                   this Registration Statement).
  -----------------------
  (1)  Filed as an exhibit to the Registrant's Registration Statement on Form S-1
       (File No. 333-11105) declared effective on October 16, 1996 and
       incorporated herein by reference.
  Page 8 of 10