ArQule Summarizes Abstracts Presented At AACR.

Pre-clinical findings support c-Met inhibition and activation of DNA damage response mechanisms as novel approaches to treating cancer

WOBURN, Mass. -- ArQule, Inc. (NASDAQ: ARQL) today announced that eleven abstracts submitted by the Company were presented at the 2007 Annual Meeting of the American Association for Cancer Research (AACR), April 14-18, 2007 in Los Angeles. The AACR abstracts are based on pre-clinical studies that provide a rationale for the Company's approaches to cancer therapy as embodied in its c-Met inhibition and DNA damage response/checkpoint activation platforms. They add significantly to the database of knowledge related to the Company's clinical-stage products, ARQ 197 and ARQ 501, and represent a broad scope of findings from in vitro (cell line) and in vivo (animal) experiments. Summaries of these studies are presented below.

ArQule expects to announce data from ongoing clinical trials with products based on these approaches to cancer therapy at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO), June 1-5, 2007, as well as in data disclosures expected in mid-2007.

Summaries of AACR abstracts

ARQ 197 / c-Met inhibition

1. ARQ 197, a highly selective small molecule inhibitor of c-Met, inhibits invasive and metastatic growth of cancer cells: Treatment with the selective c-Met inhibitor, ARQ 197, was shown to inhibit the invasion and migration of a human lung cancer cell line in response to HGF (hepatocyte growth factor), while ectopic expression of c-Met imparted an invasive phenotype to a normally non-invasive cell line that does not express c-Met.

2. ARQ 197, a highly selective small molecule inhibitor of c-Met, with selective antitumor properties in a broad spectrum of human cancer cells: Data collected to date demonstrated the high selectivity of ARQ 197 for c-Met when profiled biochemically against a panel of 230 kinases. A potent inhibitor of c-Met in multiple human cancer lines, ARQ 197 also was shown to inhibit growth of human tumor xenografts in rodents.

3. Broad spectrum anti-cancer activity of ARQ 197, a highly selective oral c-Met inhibitor, in multiple xenograft models: In four human tumor xenograft models in athymic mice, including breast cancer, prostate cancer, colon cancer and pancreatic cancer, oral treatment with ARQ 197 inhibited tumor growth, with no observed adverse effects.

4. Anti-metastatic activity of ARQ 197, a highly selective oral small molecule inhibitor of c-Met, in experimental metastatic models of colon cancer: Treatment with ARQ 197 in animal models was shown to block metastasis of human colon carcinoma to the liver and lungs.

5. Evaluation of biomarkers for HGFR/c-Met inhibitor ARQ 197 in a human xenograft model: The effects of ARQ 197 on biomarkers related to c-Met inhibition were examined, and data indicated that phosphorylated c-Met and downstream signal transducers may be employed in the clinical development of the c-Met inhibitor, ARQ 197.

ARQ 501 / Checkpoint pathway activation

6. Functional chemogenomics approach to identify checkpoint pathway activators against cancer: In a cell-based study, activation of the checkpoint pathway mediators, phosphorylated Chk2 and E2F1, was quantitatively evaluated using functional chemogenomics and correlated to the killing of a broad spectrum of human tumor cells.

7. Pharmacokinetics of a novel PGA-ARQ 501 conjugate in mouse xenografts: Findings demonstrated that a new ARQ 501 prodrug compound with improved pharmacokinetic properties can deliver ARQ 501 into human tumor xenografts with enhanced permeability and retention in tumor tissue.

8. Mass balance and characterization of the metabolites of ARQ 501 ([eth]-lapachone), a checkpoint pathway activator in clinical development: Findings showed that ARQ 501 was rapidly excreted after administration in animals and that metabolism of this compound was adequately predicted by in vitro assays.

9. Pharmacodynamic biomarkers for checkpoint pathway activator ARQ501 in a human colon xenograft model: A panel of biomarkers was analyzed in a xenograft model to provide the basis for monitoring the therapeutic effects of ARQ 501 in human clinical trials.

10. Selective induction of necrotic cell death in cancer cells by [eth]-lapachone through activation of DNA damage response pathway: Previously published data showed that activation of E2F1-mediated DNA damage response pathways by ARQ 501 resulted in apoptosis. This study showed that transient activation of PARP1 by ARQ 501 can lead to selective necrotic cell death in a variety of cancer cells.

11. Selective killing of cancer cells by activation of human checkpoint kinase 2: This study demonstrated that activation of the human checkpoint kinase 2 biological pathway, without DNA damage, results in selective toxicity in multiple malignantly transformed cell lines but not in non-cancerous cells.

About ArQule

ArQule, Inc. is a biotechnology company engaged in the research and development of next-generation, small-molecule cancer therapeutics. The Company's targeted, broad-spectrum products and research programs are designed to affect key biological processes that are central to cancer. ArQule's lead clinical-stage products have been generated from two scientific platforms: Cancer Survival Protein modulation and Activated Checkpoint Therapy([R]) (ACT). The Cancer Survival Protein modulation platform has generated a clinical-stage product designed to inhibit a molecule known as c-Met, which plays multiple roles in cancer cell growth, survival, invasion, angiogenesis and metastasis. The ACT platform is designed to kill cancer cells selectively while sparing normal cells through direct activation of DNA damage response/checkpoint pathways. The Company's lead ACT program, based on the E2F-1 pathway, is partnered with Roche. For more information, please visit www.arqule.com.

This press release contains forward-looking statements regarding the Company's clinical-stage development programs, ARQ 197, ARQ 501 and ARQ 171. These statements are based on the Company's current beliefs and expectations, and are subject to risks and uncertainties that could cause actual results to differ materially. Positive information about pre-clinical studies or early stage clinical trial results does not ensure that later stage or larger scale clinical trials will be successful. For example, ARQ 197, ARQ 501 and ARQ 171 may not demonstrate promising therapeutic effect; in addition, they may not demonstrate an appropriate safety profile in current or later stage or larger scale clinical trials as a result of known or as yet unanticipated side effects. The results achieved in ongoing or later stage trials may not be sufficient to meet applicable regulatory standards. Problems or delays may arise during clinical trials or in the course of developing, testing or manufacturing these compounds that could lead the Company or its partner to discontinue development. Even if later stage clinical trials are successful, the risk exists that unexpected concerns may arise from analysis of data or from additional data or that obstacles may arise or issues be identified in connection with review of clinical data with regulatory authorities or that regulatory authorities may disagree with the Company's view of the data or require additional data or information or additional studies. In addition, the planned timing of initiation and completion of clinical trials for ARQ 197 and ARQ 501 are subject to the ability of the Company to enroll patients, enter into agreements with clinical trial sites and investigators, and other technical hurdles and issues that may not be resolved. Drug development involves a high degree of risk. Only a small number of research and development programs result in the commercialization of a product. For more detailed information on the risks and uncertainties associated with the Company's drug development and other activities see the Company's periodic reports filed with the Securities and Exchange Commission. The Company does not undertake any obligation to publicly update any forward-looking statements.