A potent and orally bioavailable Hsp90 inhibitor
CH5138303 is an inhibitor of Hsp90 with Kd value of 0.48 nM [1].
Heat shock protein 90 (HSP90) is a chaperone protein that stabilizes proteins against heat stress, assists proteins to fold properly and aids in protein degradation. Also, HSP90 stabilizes proteins required for tumor growth.
CH5138303 is an orally available Hsp90 inhibitor. CH5138303 showed improved water solubility with 646 μM and high affinity against Hsp90α with Kd value of 0.48 nM. In NCI-N87 cells, CH5138303 decreased the protein level and phosphorylation of Hsp90 target proteins such as Raf1, AKT, EGFR and HER2 [1].
In mice, CH5138303 exhibited high plasma clearance, oral bioavailability and total systemic exposure (AUC). In mice bearing human NCI-N87 gastric cancer xenograft model, CH5138303 exhibited potent antitumor efficacy with tumor growth inhibition (TGI) of 136% and ED50 value of 3.9 mg/kg [1].
Reference:
[1].? Suda A, Kawasaki K, Komiyama S, et al. Design and synthesis of 2-amino-6-(1H,3H-benzo[de]isochromen-6-yl)-1,3,5-triazines as novel Hsp90 inhibitors. Bioorg Med Chem, 2014, 22(2): 892-905.
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