Paper in Cancer Research Further Validates Ambit Biosciences' KinomeScan Kinase Profiling Platform
SAN DIEGO -(BUSINESS WIRE) - January 16, 2006 - Ambit Biosciences today announced the publication in the January 15, 2006 issue of the journal Cancer Research of a crystal structure that explains why the Aurora kinase inhibitor VX-680 is active against Gleevec(r) (imatinib)-resistant forms of the kinase BCR-ABL, including the T315I mutant variant. The T315I mutation is the most common drug-resistant mutation in chronic myelogenous leukemia (CML) and confers resistance not only to Gleevec, but to all second generation BCR-ABL inhibitors currently in clinical development. The interaction between VX-680 and BCR-ABL variants was initially identified using Ambit's proprietary KinomeScan kinase profiling platform.
The Cancer Research study was published in an article entitled "Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680" (Matthew A. Young, et al.) and is available online this week. The binding profile of VX-680 across a large panel of kinases including ABL(T315I), determined with KinomeScan technology, was published previously by Ambit scientists in the August 2, 2005 issue of the Proceedings of the National Academy of Sciences (PNAS) ("Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases" (Todd A. Carter, et al.)).
"These data demonstrate that KinomeScan's profile of VX-680 was right on target," said Scott Salka, Chief Executive Officer of Ambit. "This study also highlights the versatility of KinomeScan, which rapidly identifies, characterizes and quantifies kinase-small molecule interactions. It can be utilized throughout the drug discovery and development continuum, from specificity and lead optimization to the identification of new indications for clinical compounds such as VX-680. Additionally, Ambit has used KinomeScan to discover next-generation kinase inhibitors, which we are currently evaluating in preclinical studies, including a compound that specifically targets the T315I mutation."
The Cancer Research study was led by Matthew Young, Ph.D., and John Kuriyan, Ph.D., of the Howard Hughes Medical Institute, University of California, Berkeley, in collaboration with Neil Shah, M.D., Ph.D., and Charles Sawyers, M.D., of the Howard Hughes Medical Institute at the University of California, Los Angeles, and Ambit Biosciences. The study describes the crystal structure of VX-680 bound to the catalytic domain of BCR-ABL containing a mutation that causes Gleevec resistance but is inhibited by VX-680 in vitro. The paper also demonstrates that VX-680 inhibits BCR-ABL activity in cells derived from patients carrying the T315I mutation and that it retains activity against T315I in vitro. VX-680 is currently being evaluated in a Phase 1 clinical trial for cancer by Vertex Pharmaceuticals and Merck.
About Ambit Biosciences
Ambit Biosciences is a privately-held biopharmaceutical company engaged in the discovery and development of small molecule kinase inhibitors for the treatment of cancer. Ambit plans to initiate clinical trials with its lead FLT-3 inhibitor for the treatment of Acute Myeloid Leukemia in 2006. Ambit's proprietary kinase profiling technology, KinomeScan, is designed to be integrated across all stages of the drug discovery and development process and has been validated through collaborations with Roche, Bristol-Myers Squibb Company, GlaxoSmithKline, Pfizer and others. Ambit has raised a total of more than $56 million from investors including Perseus-Soros Biopharmaceutical Fund, Forward Ventures, Roche Venture Fund, Avalon Ventures, GIMV NV, MDS Capital, Genechem and Bristol-Myers Squibb Company.