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Exelixis, Inc. Message Board

  • hbomb57108 hbomb57108 May 9, 2013 12:30 PM Flag

    MGCD265 from Methylgene similar to Cabozantinib

    Methylgene intends to trade on Nasdaq under name Mirati

    Here is target and preclinical rationale from website

    MGCD265 is a rationally designed, orally administered small molecule kinase inhibitor that targets the receptor tyrosine kinases (RTKs) Met, VEGFR 1,2,3 and Axl, as well as Tie2 and Ron. These kinases play key roles in tumor development, survival and metastasis as well as the inappropriate formation of blood vessels (angiogenesis) that nourish the tumors.
    The Met receptor is a protein that is found on the cell’s surface. When not properly regulated (i.e. over active) it plays a key role in the growth, survival and metastasis of various types of cancers such as non-small cell lung, gastric, prostate, colorectal, bladder, breast and ovarian cancers.
    The Met signaling pathway is very important in cancer, as Met has been shown to be a vital escape pathway for tumor cells. When tumor cells are attacked by some cancer therapies, Met helps the tumor cells to escape death. MGCD265′s inhibition of both the Met and VEGFR targets appears to effectively block the Met-driven escape mechanism used by tumor cells when treated with other targeted cancer therapies.
    Axl is a receptor tyrosine kinase that has recently become the subject of increased scientific and clnical interest. Studies have shown that Axl expression is correlated with clinical stage and lymph node status in non-small cell lung cancer, and involved in the mechanism of resistance to EGFR inhibitors. Axl may be a significant driver in renal cell carcinoma, hepatocellular carcinoma and other tumors.

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