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Exelixis Files IND Application for XL019, a Novel Anticancer Compound Targeting the JAK/STAT Signaling Pathway

30 May 2007 - Exelixis, Inc. announced that it has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration for XL019. The compound has shown to be a potent, selective and orally available small molecule inhibitor of the cytoplasmic tyrosine kinase JAK2, in preclinical studies. Activating mutations in JAK2 are frequently observed in patients with myeloproliferative disorders such as myelofibrosis, polycythemia vera and essential thrombocythemia. JAK2 activity is also upregulated via multiple mechanisms in many lymphomas and solid tumors.
 
XL019 is a selective inhibitor of the cytoplasmic tyrosine kinase JAK2. JAK2 is activated by cytokine and growth factor receptors and phosphorylates members of the STAT family of inducible transcription factors. Activation of the JAK/STAT pathway promotes cell growth and survival, and is a common feature of human tumors. JAK2 is activated by mutation in the majority of patients with polycythemia vera, essential thrombocythemia and myelofibrosis and appears to drive the inappropriate expansion of blood cells observed in these conditions. JAK2 also plays a role in immune cell function and inhibitors may therefore have utility in a broad spectrum of inflammatory diseases. XL019 is a potent and selective JAK2 inhibitor with favorable pharmacodynamic properties and preclinical safety profile.