mfh 290

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.

LEO 134310 是一种选择性非甾体糖皮质激素受体 (GR) 激动剂，优化用于局部治疗。LEO 134310 在 GR 结合试验中显示出高亲和力(EC50为 14 nM)。LEO 134310 可用于皮肤病。