CEP-33779

CEP-33779 is a highly selective, orally active, small-molecule inhibitor of JAK2. CEP-33779 (< 3 μM) inhibits phosphorylation of downstream target signal transducer and activator of transcription 5 (pSTAT5) of JAK2 in a concentration dependent manner in HEL92 cells. CEP-33779 induced regression of established colorectal tumors, reduced angiogenesis, and reduced proliferation of tumor cells. CEP-33779 results in reduced bone degradation, reduced tissue destruction, and reduced osteoarthritis in dose-dependent manner in CAIA or CIA mice. CEP-33779 suppressed growth of colorectal tumors by inhibiting the IL-6/JAK2/STAT3 signaling. Treatment with CEP-33779 extended survival and reduced splenomegaly/lymphomegaly. Several serum cytokines were significantly decreased upon treatment including IL-12, IL-17A, IFN-α, IL-1β, and TNF-α.