Science
CYT387 is a potent, selective JAK1/JAK2 inhibitor designed to suppress the over-activity of the mutant JAK2.
The compound possesses an excellent selectivity and safety profile with minimal off-target activities, favorable pharmacokinetic properties, a clean toxicological profile and the prospect of limited drug/drug interactions. Preliminary data using samples derived from MPN patients have shown promising activity in suppressing the over-activity of the JAK2V617F mutant enzyme.
JAK2 in Myeloproliferative Neoplasms
MPNs are debilitating, and potentially fatal, diseases of blood cell production. MPNs such as polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are disorders for which there are limited and poorly efficacious therapeutic options. A genetic mutation in the JAK2 enzyme, which results in constitutive activity of the enzyme, has been shown present in >95% of patients with PV, ~50% of patients with ET and ~50% of patients with MF. In an in vivo model of MPNs, CYT387 showed excellent activity, essentially reversing a number of the hallmarks of the disease.
More information about myeloproliferative neoplasms can be found at www.mpdfoundation.org.
JAK2 in Cancer
JAK2 and its related biochemical pathways are now known to play a key role in the proliferation of certain types of cancer cells such as prostate, breast, head & neck, lung, ovarian, renal cell, glioma, pancreatic and liver cancers, and hematological cancers such as multiple myeloma, lymphoma and leukemia. Preclinical research is underway to examine the activity of CYT387 in these indications.
Manuscripts
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Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood June 2010; 115(25): 5232-5240 (First Edition Paper published online April 12, 2010) |
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Burns CJ, et al. Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs). Bioorg Med Chem Lett 2009 Oct; 19(20): 5887-5892 |
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Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia 2009; 23: 1441-1445 |
Posters and Abstracts
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Burns CJ. A novel, potent and selective dual inhibitor of JAK1 and JAK2 for treatment of myeloproliferative neoplasms. 2010 New Directions in Leukaemia Research (NDLR), Abstract |
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Burns CJ. A novel, potent and selective dual inhibitor of JAK1 and JAK2 for treatment of myeloproliferative neoplasms and cancer. 2010 Lorne Cancer Conference, Abstract |
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Bumm TG, et al. Effects of CYT387, a Potent Novel JAK2 Inhibitor on JAK2-V617F Induced MPD. 2008 ASH Annual Meeting, Abstract 856 |
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Wilks A, et al. A novel JAK2 inhibitor for the treatment of myeloproliferative disorders. 2008 AACR Annual Meeting, Abstract 4880 |
