CEP-33779

2 years -80 in solvent

Orally administered twice daily

55 mg/kg

1.8 nM [1], 1.8 nM [1], 1.8 nM [1], 1.8 nM [1], 1.8 nM [1], 1.8 nM [1]

CEP33779 orally administrated with 55 mg/kg inhibits phosphorylation of STAT5 in HEL92 tumor extracts from HEL92 xenograft mice. CEP33779 orally administered twice daily at dose of 55 mg/kg reduces mean paw edema and clinical scores in mice with collagen-antibody induced arthritis (CAIA) or collagen-induced arthritis (CIA). CEP33779 orally administered twice daily at dose of 55 mg/kg totally inhibits paw phospho-STAT3 expression in CAIA or CIA mice, associated with decreased cytokines including IL-12, IFNgamma, IL-2, IL-1beta, TNFalpha and GM-CSF. CEP33779 results in reduced bone degradation, reduced tissue destruction, and reduced osteoarthritis in dose-dependent manner in CAIA or CIA mice. [1] CEP33779 orally administrated at 100 mg/kg extends survival and reduces splenomegaly/lymphomegaly in MRL/lpr systemic lupus erythematosus mice, thus protect mice from developing glomerulonephritis. CEP33779 orally administrated at 100 mg/kg decreases several SLE-associated proinflammatory cytokines and reduces levels of a bone resorption biomarker associated with increased osteoclast activity in MRL/lpr systemic lupus erythematosus mice. [2] CEP33779 orally administered twice daily at dose of 55 mg/kg induces regression of established colorectal tumors, reduces angiogenesis, and reduces proliferation of tumor cells in a mouse model of colitis-induced colorectal cancer. Tumor regression correlated with inhibition of STAT3 and NF-kappaB (RelA/p65) activation, and decreased the expression of proinflammatory, tumor-promoting cytokines interleukin (IL)-6 and IL-1beta. [3]

CEP33779 is a selective JAK2 inhibitor with IC50 of 1.8 nM, >40- and >800-fold versus JAK1 and TYK2.