2088715-91-5
英文名稱
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
2088715-91-5 結(jié)構(gòu)式
基本信息
英文別名
MFH2902-Propenamide, N-[4-[[(3R)-3-[[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]amino]-1-piperidinyl]carbonyl]phenyl]-
物理化學(xué)性質(zhì)
密度1.31±0.1 g/cm3(Predicted)
酸度系數(shù)(pKa)13.29±0.70(Predicted)
形態(tài)Solid
顏色White to off-white
應(yīng)用領(lǐng)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.