CH5138303 is a triazine Hsp90 inhibitor. CH5138303 binds to the N-terminus of Hsp90α (Kd = 0.52 nM) and inhibits growth of HCT116 and NCI-N87 human tumor cell lines in vitro (IC50s = 89 and 66 nM, respectively). CH5138303 also inhibits growth of human NCI-N87 gastric cancer xenografts (ED50 = 3.9 mg/kg) and displays high oral bioavailability in mice.
CH5138303 is a potent and orally active Hsp90 inhibitor. CH5138303 shows high binding affinity for N-terminal Hsp90α, with Kd of 0.52 nM. CH5138303 shows potent anti-proliferative activity against human cancer cell lines (HCT116 and NCI-N87), with IC50 values of 0.098 and 0.066 μM, respectively. CH5138303 shows high oral bioavailability in mice (F=44.0%). CH5138303 shows potent antitumor efficacy in a human NCI-N87 gastric cancer xenograft model[1][2].
CH5138303 (SCID mice bearing NCI-N87 cells, 0-50 mg/kg, Orally, once daily for 11 days) shows potent antitumor efficacy with TGI (tumor growth inhibition) of 136% and a median effective dose (ED50) of 3.9 mg/kg without significant loss of body weight[1].
[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.
