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Method To Treat Numerous Types Of Cancer Using Small Molecule Inhibitors

Background:
The National Cancer Institute's Urologic Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize small molecule inhibitors of the c-Met signaling pathway.

Technology:
A key defect in many types of cancer is unregulated activation of an enzyme known as c-Met.  Aberrant c Met signaling is documented in a wide variety of cancers and occurs via several mechanisms. This invention describes novel small molecule inhibitors of c-Met signaling.  The small molecules selectively bind to c-Met and have an IC50 in the micromolar range. The small molecules belong to two different families.  One family of small molecules reduces the level of c Met expression via receptor down-regulation and blocks ATP binding.  The other family of small molecules block ATP binding without inducing receptor down-regulation.

Further R&D Needed:

• Preclinical cell-free and cell-based SAR studies to improve selectivity and potency.

• Preclinical biological studies in cultured cell and animal models.

• Preclinical PK and toxicological studies in animals.

• Ability to develop therapeutics for numerous types of cancers associated with aberrant c-Met signaling including bladder, breast, cervical, colorectal, endometrial, esophageal, gastric, head and neck, kidney, liver, lung, nasopharyngeal, ovarian, pancreatic, prostate and thyroid cancers.

• Ability to develop therapeutics for hematological malignancies such as acute myelogenous leukemia, adult T cell leukemia, chronic myeloid leukemia, lymphomas and multiple myeloma