KW-2478 819812-04-9

KW2478
分子式：C30H42N2O9   分子量：574.66
 
產(chǎn)品描述
KW-2478 是非Ansamycin的HSP90抑制劑，IC50為3.8 nM。
靶點(diǎn)
HSP90
         
IC50
3.8 nM
         
體外研究
KW-2478 inhibits the binding of bRD to Hsp90α with IC50 of 3.8 nM. KW-2478 degradates the Hsp90 client proteins, including FGFR3 and IGF-1Rβand c-Raf-1. KW-2478 reduces the level of phosphorylated Erk1/2. KW-2478 induces apoptosis by cleavage of PARP, a substrate of caspase-3 In U266 cells,. KW-2478 has Time dependency of antiproliferative activity, consecutive drug exposure for at least 12 hours is necessary to to exert potent antitumor activity. KW-2478 downregulates the translocation products of IgH locus. KW-2478 inhibits the transcription of c-Maf and cyclin D1 genes by mainly suppressing the function of Cdk9.KW-2478 has potent and broad growth inhibitory activities against various cell lines, KW-2478 inhibites cancer cell growth in all cell lines, with EC50 of 101-252 nM, 81.4-91.4 nM and 120-622 nM for B-cell lymphoma, mantle cell lymphoma and multiple myeloma, respectively. KW-2478 also shows potent growth inhibitory activity in primary CLL and NHL cells with EC50 of 40-170 nM and 200-400 nM, respectively.
體內(nèi)研究
KW-2478 suppresses tumor growth and induces the degradation of client proteins in tumors in NCI-H929 s.c. inoculated model at doses of 100 mg/kg or more. KW-2478 reduces both serum M protein and MM tumor burden in the bone marrow in OPM-2/GFP i.v. inoculated mouse model at doses of 100 mg/kg.
溶解性
DMSO 115 mg/mL，水 <1 mg/mL，乙醇 3 mg/mL
穩(wěn)定性
2年 -20°C粉狀，6月-80°C溶于DMSO