product name CH5138303
Description: CH5138303 is a novel, potent, orally available Hsp90 inhibitor with Kd of 0.48 nM. CH5138303 showed high binding affinity for N-terminal Hsp90α (Kd=0.52nM) and strong in vitro cell growth inhibition against human cancer cell lines (HCT116 IC50=0.098μM, NCI-N87 IC50=0.066μM) and also displayed high oral bioavailability in mice (F=44.0%) and potent antitumor efficacy in a human NCI-N87 gastric cancer xenograft model (tumor growth inhibition=136%).
References: Bioorg Med Chem. 2014 Jan 15;22(2):892-905.
415.9
Formula
C19H18ClN5O2S
CAS No.
959763-06-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 83 mg/mL (199.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: CH5138303 shows high affinity to Hsp90αand potent cell growth inhibitory activity against an HCT116 colorectal cancer cell line and an NCI-N87 gastric cancer cell line with IC50 of 98 nM and 66 nM, respectively. Besides, CH5138303 also demonstrates liver microsomal stability. Kinase Assay: 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. Cell Assay: 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. |
|---|---|
| In Vivo | CH5138303 (50 mg/kg p.o.) displays high oral bioavailability in mice and produces potent antitumor efficacy in a human NCI-N87 gastric cancer xenograft model. |
| Animal model | Human NCI-N87 gastric cancer xenograft model. |
| Formulation & Dosage | 50 mg/kg; p.o. |
| References | Bioorg Med Chem. 2014 Jan 15;22(2):892-905. |
