《Discovery of MFH290: A Potent and Highly Selective Covalent Inhibitor for Cyclin-Dependent Kinase 12/13》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Liu, Yao; Hao, Mingfeng; Leggett, Alan L.; Gao, Yang; Ficarro, Scott B.; Che, Jianwei; He, Zhixiang; Olson, Calla M.; Marto, Jarrod A.; Kwiatkowski, Nicholas P.; Zhang, Tinghu; Gray, Nathanael S.. Quality Control of 5-Bromothiazol-2-amine The article mentions the following:
Genetic depletion of cyclin-dependent kinase 12 (CDK12) or selective inhibition of an analog-sensitive CDK12 reduces DNA damage repair gene expression, but selective inhibition of endogenous CDK12 is difficult. Here, we report the development of MFH290(I), 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.5-Bromothiazol-2-amine(cas: 3034-22-8Quality Control of 5-Bromothiazol-2-amine) was used in this study.
5-Bromothiazol-2-amine(cas: 3034-22-8) belongs to anime. Many important products require amines as part of their syntheses. Methylamine is utilized in the production of the analgesic meperidine (trade name Demerol) and the photographic developer Metol (trademark), and dimethylamine is used in the synthesis of the antihistamine diphenhydramine (trade name Benadryl), the solvent dimethylformamide (DMF), and the rocket propellant 1,1-dimethylhydrazine. The synthesis of the insect repellent N,N-diethyl-m-toluamide (DEET) incorporates diethylamine while that of the synthetic fibre Kevlar requires aromatic amines.Quality Control of 5-Bromothiazol-2-amine
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica