KW-2478 _HSP 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEKW-2478Cat. No.: HY-13468CAS No.: 819812-04-9分式: CHNO分量: 574.66作靶點(diǎn): HSP作通路: Cell Cycle/DNA Damage; Metabolic Enzyme/Protease儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 83.3 mg/mL (144.9

2、6 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.7402 mL 8.7008 mL 17.4016 mL5 mM 0.3480 mL 1.7402 mL 3.4803 mL10 mM 0.1740 mL 0.8701 mL 1.7402 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 KW-2478種 Hsp90 抑制劑，IC50 值為 3.8 nM，對(duì)多種類

3、液腫瘤細(xì)胞具有抗腫瘤活性。IC50 & Target HSP903.8 nM (IC50)體外研究KW-2478 is an inhibitor of Hsp90, with an IC50 of 3.8 nM for Hsp90. KW-2478 shows anti-proliferative1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEactivity against multiple myeloma (MM) and non-Hodgkins lymphoma (NHL), with GI50s of 0.30 M (OPM-2/GF

4、P), 0.34 M (KMS-11), 0.39 M (RPMI 8226), 0.12 M (NCI-H929), 0.36 M (Raji), 0.098 M (SR), and0.33 M M (SC-1). KW-2478 also inhibits the transcription of c-Maf and Cyclin D1 genes by mainlysuppressing the function of Cdk9 1.體內(nèi)研究 KW-2478 (25-200 mg/kg, i.v.) inhibits tumor growth in combined immunodefi

5、ciency (SCID) mice bearing NCI-H929 cells, without body weight loss. KW-2478 (100 mg/kg, i.v.) causes degradation of the Hsp90 clientproteins (IGF-1R, c-Raf-1, Cdk9) levels and dephosphorylated Erk1/2 proteins in NCI-H929 tumors of mice1.PROTOCOLCell Assay 1 The cells are plated into 96-well plates

6、and treated with KW-2478. After 72 hours of cultivation, cell viability isdetermined using WST-1. WST reagent is added to the wells, followed by incubation for 4 hours at 37C.After that, the absorbance at 450 nm with reference at 650 nm is measured with a microplatespectrophotometer 1.MCE has not in

7、dependently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Severe combined immunodeficient (SCID) mice are intraperitoneally injected with anti-asialo GM1 antibody.The next day, all mice are subcutaneously inoculated with NCI-H929 cells (1107 cells

8、) suspended in PBScontaining 50% of Matrigel. After 10 days, tumor volume is measured using the Antitumor test system II, acomputer-operated system including software and instruments. SCID mice with tumors (190 to 290 mm3) areselected. After randomly grouping, saline (vehicle) or KW-2478 is intraven

9、ously administered to mice once ortwice daily for 5 days. 17-AAG is intravenously administered to mice. Tumor volume is calculated by the Anti-tumor test system II as follows: Tumor volume=DLDSDS1/2. Fourteen days after the initial administration,blood samples of each mouse are obtained, followed by

10、 measurement of serum M protein (Ig kappa chain)with Human Kappa-b&f ELISA Quantitation Kit. The statistical analysis is performed using SAS software 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Nakashima T, et al. New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shockprotein 90 inhibitor, in multiple myeloma cells. Clin Cancer Res. 2010 May 15;16(10):2792-802.McePdfHeightCaution: Product has not been f