2088715-91-5
中文名称
化合物 MFH290
英文名称
2-Propenamide, N-[4-[[(3R)-3-[[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]amino]-1-piperidinyl]carbonyl]phenyl]-
CAS
2088715-91-5
分子式
C26H31N5O3S2
分子量
525.69
MOL 文件
2088715-91-5.mol
结构式
基本信息
中文别名
化合物 MFH290
英文别名
MFH290
2-Propenamide, N-[4-[[(3R)-3-[[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]amino]-1-piperidinyl]carbonyl]phenyl]-
2-Propenamide, N-[4-[[(3R)-3-[[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]amino]-1-piperidinyl]carbonyl]phenyl]-
物理化学性质
| 密度 | 1.31±0.1 g/cm3(Predicted) |
| 酸度系数(pKa) | 13.29±0.70(Predicted) |
| 形态 | Solid |
| 颜色 | White to off-white |
应用领域
用途一
MFH290 is a novel cysteine (Cys)-directed covalent inhibitor of CDK12/13. MFH290 forms a covalent bond with Cys-1039 of CDK12, exhibits excellent kinome selectivity, inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II), and reduces the expression of key DNA damage repair genes. Importantly, these effects were demonstrated to be CDK12-dependent as mutation of Cys-1039 rendered the kinase refractory to MFH290 and restored Pol II CTD phosphorylation and DNA damage repair gene expression. Consistent with its effect on DNA damage repair gene expression, MFH290 augments the antiproliferative effect of the PARP inhibitor olaparib.
常见问题列表
概述
MFH290 是一种有效的高选择性细胞周期蛋白依赖性激酶 12/13 (CDK12/13) 共价抑制剂。MFH290 与 CDK12 的 Cys-1039 形成共价键，表现出优异的 kinome 选择性，抑制 -聚合酶II (Pol II) C-terminal domain (CTD)中丝氨酸-2的磷酸化。MFH290用于癌症研究。