| Identification | Back Directory | [Name]
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 | [Synonyms]
MFH290
2-Propenamide, N-[4-[[(3R)-3-[[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]amino]-1-piperidinyl]carbonyl]phenyl]- | [Molecular Formula]
C26H31N5O3S2 | [MOL File]
2088715-91-5.mol | [Molecular Weight]
525.69 |
| Hazard Information | Back Directory | [Description]
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. | [Uses]
MFH290 is a potent and highly selective cyclin-dependent kinase 12/13 (CDK12/13) covalent inhibitor. MFH290 forms a covalent bond with Cys-1039 of CDK12 and exhibits excellent kinome selectivity and inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II). MFH290 is used for cancer research[1]. | [References]
[1] Yao Liu, et al. Discovery of MFH290: A Potent and Highly Selective Covalent Inhibitor for Cyclin-Dependent Kinase 12/13. J Med Chem. 2020 Jul 9;63(13):6708-6726. DOI:10.1021/acs.jmedchem.9b01929
[2] Yao Liu, et al. Discovery of MFH290: A Potent and Highly Selective Covalent Inhibitor for Cyclin-Dependent Kinase 12/13. J Med Chem. 2020 Jul 9;63(13):6708-6726. DOI:10.1021/acs.jmedchem.9b01929 |
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