KW-2478CAS号: 819812-04-9分子式: C30H42N2O9分子量: 574.66描述纯度储存/保存方法别名外观可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)
产品描述 | |
描述 |
KW-2478 is a novel non-ansamycin potent Hsp90 inhibitor with an IC50 of 3.8 nM. KW-2478 is a novel non-purine analogue antagonist for Hsp90. KW-2478 suppressed the binding of bRD to HSP90α in concentration-dependent manner. KW-2478 indicated a potent anti-cancer activity both in vitro and in vivo. KW-2478 clearly prevented cancer cell growth in all cell lines, with EC50 of 101-252, 81.4-91.4 and 120-622 nM for B-cell lymphoma, mantle cell lymphoma and multiple myeloma, respectively. KW-2478 also showd potent growth inhibitory activity in primary CLL (n=3) and NHL (n=2) cells with EC50 of 40-170 nM and 200-400 nM, respectively. KW-2478 depleted the Hsp90 client Cdk9, a transcriptional kinase, and the phosphorylated 4E-BP1, a translational inhibitor. Both inhibitory effects of KW-2478 on such transcriptional and translational pathways were shown to reduce c-Maf and cyclin D1 expression. In NCI-H929 s.c. inoculated model, KW-2478 displayed a significant inhibition of tumor growth and induced the degradation of client proteins in tumors. |
纯度 |
>98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
别名 |
KW2478
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外观 |
固体粉末
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可溶性/溶解性 |
Ethanol :3 mg/mL (5.22 mM)
DMSO :106 mg/mL (184.5 mM) |
生物活性 | |
靶点 |
HSP90
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In vitro(体外研究) |
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. .
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In vivo(体内研究) |
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.
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分子结构图