819812-04-9
中文名稱
KW-2478
英文名稱
KW-2478
CAS
819812-04-9
分子式
C30H42N2O9
分子量
574.662
MOL 文件
819812-04-9.mol
更新日期
2024/12/23 17:38:58
819812-04-9 結(jié)構(gòu)式
基本信息
中文別名
2-乙基-3,5-二羥基-N,N-雙(2-甲氧基乙基)-6-[3-甲氧基-4-[2-(4-嗎啉基)乙氧基]苯甲?；鵠苯乙酰胺2-(2-乙基-3,5-二羥基-6-(3-甲氧基-4-(2-嗎啉代乙氧基)苯甲酰基)苯基)-N,N-雙(2-甲氧基乙基)乙酰胺
英文別名
CS-287KW-2478
KW-2478 USP/EP/BP
KW2478
KW-2478
KW 2478.
2-(2-Ethyl-3,5-dihydroxy-6-(3-methoxy-4-(2-morpholinoethoxy)benzoyl)phenyl)-N,N-bis(2-methoxye
2-(2-ethyl-3,5-dihydroxy-6-(3-methoxy-4-(2-morpholinoethoxy)benzoyl)phenyl)-N,N-bis(2-methoxyethyl)acetamide
2-Ethyl-3,5-dihydroxy-N,N-bis(2-methoxyethyl)-6-[3-methoxy-4-[2-(4-morpholinyl)ethoxy]benzoyl]benzeneacetamide
2-[2-ethyl-3,5-dihydroxy-6-[3-methoxy-4-(2-morpholin-4-ylethoxy)benzoyl]phenyl]-N,N-bis(2-methoxyethyl)acetamide
Benzeneacetamide, 2-ethyl-3,5-dihydroxy-N,N-bis(2-methoxyethyl)-6-[3-methoxy-4-[2-(4-morpholinyl)ethoxy]benzoyl]-
2-Ethyl-3,5-dihydroxy-N,N-bis(2-methoxyethyl)-6-[3-methoxy-4-[2-(4-morpholinyl)ethoxy]benzoyl]benzeneacetamide KW2478
所屬類別
生物化工：HSP e.g. HSP90 抑制劑常見問題列表
生物活性
KW-2478是一種非Ansamycin的HSP90抑制劑，IC50為3.8 nM。Phase 1。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.靶點(diǎn)
| Target | Value |
|
HSP90
() | 3.8 nM |
體外研究
KW-2478抑制bRD與Hsp90α的結(jié)合，IC50為3.8 nM。KW-2478降解Hsp90受體蛋白，包括FGFR3，IGF-1Rβ和c-Raf-1。KW-2478降低磷酸化Erk1/2的水平。在U266細(xì)胞中，KW-2478通過PARP裂解誘導(dǎo)細(xì)胞凋亡，PARP是caspase-3的一種底物。KW-2478具有時(shí)間依賴性抗增殖活性，需要連續(xù)藥物暴露至少12小時(shí)以發(fā)揮有效的抗腫瘤活性。KW-2478下調(diào)IgH位點(diǎn)的易位產(chǎn)品。KW-2478通過主要抑制Cdk9的功能，抑制c-Maf和細(xì)胞周期蛋白D1基因的轉(zhuǎn)錄。 KW-2478對各種細(xì)胞系具有有效且廣泛的抑制活性，KW-2478在所有細(xì)胞系中抑制癌細(xì)胞生長，對B細(xì)胞淋巴瘤，套細(xì)胞淋巴瘤和多發(fā)性骨髓瘤的EC50分別為101-252 nM，81.4-91.4 nM 和120-622 nM。KW-2478也在原代CLL 和NHL細(xì)胞中表現(xiàn)出有效的生長抑制活性，EC50分別為40-170 nM和200-400 nM。
體內(nèi)研究
在NCI-H929皮下注射接種的模型中，KW-2478在100 mg/kg或更高劑量下抑制腫瘤生長，并誘導(dǎo)腫瘤中受體蛋白降解。在OPM-2/GFP靜脈注射接種的小鼠模型中，KW-2478在100 mg/kg劑量下降低骨髓中血清M蛋白質(zhì)和MM腫瘤負(fù)擔(dān)。