"目录号: HY-15343
EpigeneticsStem Cell/WntJAK/STAT Signaling-
CEP-33779是一个新颖的，选择性，有口服活性的JAK2抑制剂，IC50值为1.8±0.6 nM。
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生物活性
Description
CEP-33779 is a novel, selective, and orally bioavailable inhibitor ofJAK2with anIC50of 1.8±0.6 nM.
IC50& Target
IC50: 1.8±0.6 nM (JAK2)[1]
In Vitro
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[3].
In Vivo
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[1]. 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[2].
References
