CEP-33779 is a novel, selective, and orally bioavailable inhibitor of JAK2 with an IC50 of 1.8±0.6 nM.
IC50&Target
JAK2
1.8 nM (IC50)
JAK3
150 nM (IC50)
体外研究
CEP-33779, at nontoxic concentrations, significantly sensitizes overexpression of P-glycoprotein overexpressing multidrug resistance cells to its anticancer substrates. CEP-33779 significantly increases intracellular accumulation and decreases the efflux of doxorubicin by inhibiting the overexpression of P-glycoprotein transport function.
体内研究
CEP-33779 exhibits a favorable PK profile in nude mice, an iv half-life of 1 h, moderate distribution (Vd=2.6 L/kg), and measurable oral exposure with an estimated bioavailability of 33%. It demonstrates antitumor efficacy in the CWR22 xenograft model; oral dosing for 14 days at 30 mg/kg bid results in tumor stasis and partial regressions in 5/10 animals. CEP-33779 administration results in an almost complete shrinkage of tumors in most animals; few remaining tumor nodules were small, poorly vascularized, and had a necrotic appearance. CEP-33779 suppressed activation of NF-κB in tumors.
分子式
C24H26N6O2S
分子量
462.57
CAS号
1257704-57-6
运输条件
Room temperature in continental US; may vary elsewhere.