<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







<PAGE>   1



                                                                     Exhibit 5.1
                                                                     -----------

                               PALMER & DODGE LLP
                                ONE BEACON STREET
                              BOSTON, MA 02108-3190

                                January 9, 1997

ArQule, Inc.
300 Boston Avenue
Medford, Massachusetts 02155

     Re:  1996 Employee Stock Purchase Plan
          ---------------------------------

Ladies and Gentlemen:

     We are rendering this opinion in connection with the Registration Statement
on Form S-8 (the "Registration Statement") filed by ArQule, Inc. (the "Company")
with the Securities and Exchange Commission (the "Commission") under the
Securities Act of 1933, as amended (the "Act"), on or about the date hereof. The
Registration Statement relates to 120,000 shares (the "Shares") of the Company's
Common Stock, $0.01 par value, offered pursuant to the provisions of the
Company's 1996 Employee Stock Purchase Plan (the "Plan").

     We have examined the Amended and Restated Certificate of Incorporation of
the Company, the Amended and Restated By-laws of the Company, and originals, or
copies certified to our satisfaction, of all pertinent records of the meetings
of the directors and stockholders of the Company, the Registration Statement and
such other documents relating to the Company as we have deemed material for the
purposes of this opinion.

     In examination of the foregoing documents, we have assumed the genuineness
of all signatures
 and the authenticity of all documents submitted to us as
originals, the conformity to original documents of all documents submitted to us
as certified or photostatic copies, and the authenticity of the originals of
such latter documents.

     Based on the foregoing, we are of the opinion that the Company has duly
authorized for issuance the shares of its Common Stock covered by the
Registration Statement to be issued under the Plan, as described in the
Registration Statement, and such shares, when issued in accordance with the
terms of the Plan, will be validly issued, fully paid and nonassessable.

     We hereby consent to the filing of this opinion as a part of the
Registration Statement.

                                                     Very truly yours,

                                                     /s/ Palmer & Dodge LLP

                                                     PALMER & DODGE LLP

                                  Page 9 of 10





<PAGE>   1


                                                                    Exhibit 23.1

                       CONSENT OF INDEPENDENT ACCOUNTANTS

We hereby consent to the incorporation by reference in this Registration
Statement on Form S-8 of our report dated October 4, 1996 appearing on page F-2
of ArQule, Inc.'s Registration Statement on Form S-1 (No. 333-11105).




PRICE WATERHOUSE LLP
Boston, Massachusetts
January 8, 1997


                                  Page 10 of 10