819812-04-9
中文名称
KW-2478
英文名称
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
2025/05/06 16:15:00
819812-04-9 结构式
基本信息
中文别名
2-乙基-3,5-二羟基-N,N-双(2-甲氧基乙基)-6-[3-甲氧基-4-[2-(4-吗啉基)乙氧基]苯甲酰基]苯乙酰胺2-(2-乙基-3,5-二羟基-6-(3-甲氧基-4-(2-吗啉代乙氧基)苯甲酰基)苯基)-N,N-双(2-甲氧基乙基)乙酰胺
英文别名
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
所属类别
生物化工：HSP e.g. HSP90 抑制剂常见问题列表
生物活性
KW-2478是一种非Ansamycin的HSP90抑制剂，IC50为3.8 nM。Phase 1。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. .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.靶点
| Target | Value |
|
HSP90
() | 3.8 nM |
体外研究
KW-2478抑制bRD与Hsp90α的结合，IC50为3.8 nM。KW-2478降解Hsp90受体蛋白，包括FGFR3，IGF-1Rβ和c-Raf-1。KW-2478降低磷酸化Erk1/2的水平。在U266细胞中，KW-2478通过PARP裂解诱导细胞凋亡，PARP是caspase-3的一种底物。KW-2478具有时间依赖性抗增殖活性，需要连续药物暴露至少12小时以发挥有效的抗肿瘤活性。KW-2478下调IgH位点的易位产品。KW-2478通过主要抑制Cdk9的功能，抑制c-Maf和细胞周期蛋白D1基因的转录。 KW-2478对各种细胞系具有有效且广泛的抑制活性，KW-2478在所有细胞系中抑制癌细胞生长，对B细胞淋巴瘤，套细胞淋巴瘤和多发性骨髓瘤的EC50分别为101-252 nM，81.4-91.4 nM 和120-622 nM。KW-2478也在原代CLL 和NHL细胞中表现出有效的生长抑制活性，EC50分别为40-170 nM和200-400 nM。
体内研究
在NCI-H929皮下注射接种的模型中，KW-2478在100 mg/kg或更高剂量下抑制肿瘤生长，并诱导肿瘤中受体蛋白降解。在OPM-2/GFP静脉注射接种的小鼠模型中，KW-2478在100 mg/kg剂量下降低骨髓中血清M蛋白质和MM肿瘤负担。