CH5138303 is an orally available Hsp90 inhibitor with Kd of 0.48 nM.

HSP90 α:0.48 nM(Kd)

CH5138303在Hsp90α上表现出高亲和力，并对HCT116结肠癌细胞株和NCI-N87胃癌细胞株显示出强大的细胞生长抑制活性，其IC50分别为98 nM和66 nM。此外，CH5138303还展示了在肝微粒体的稳定性。[1]

CH5138303（50mg/kg，口服）在小鼠中展现出高口服可用性，并在人类NCI-N87胃癌异种移植模型中显示出强大的抗肿瘤效力。[1]

Surface plasmon resonance direct binding assay for Hsp90α: Measurements are performed on a Biacore2000 at a flow rate of 30 μL/min, 25 °C in 50 mM Tris-based saline, pH 7.6, 0.005% Tween20 and 1% DMSO. Biotinylated N-terminal Hsp90α (9–236) is coupled on a streptavidin-coated surface of a sensorchip to a density of ca. 2000 RU.

HCT116 cell line and NCI-N87 cell line are cultured according to the supplier's instructions. Cells suspended in a medium are added to solutions containing various concentrations of the test substance, and the cells are cultured at 37 °C in 5% CO2. Four days later, Cell Counting Kit-8 solution is added and absorbance at 450 nm is measured with Microplate-Reader iMark. Antiproliferative activity is calculated by the formula (1?T/C) × 100 (%), where T represents the absorbance of drug-treated cells and C that of untreated control cells at 450 nm. The 50% inhibition concentration (IC50) values are calculated using Microsoft Excel 2007.(Only for Reference)