The author of 《A chemoproteomic strategy for direct and proteome-wide covalent inhibitor target-site identification》 were Browne, Christopher M.; Jiang, Baishan; Ficarro, Scott B.; Doctor, Zainab M.; Johnson, Jared L.; Card, Joseph D.; Sivakumaren, Sindhu Carmen; Alexander, William M.; Yaron, Tomer M.; Murphy, Charles J.; Kwiatkowski, Nicholas P.; Zhang, Tinghu; Cantley, Lewis C.; Gray, Nathanael S.; Marto, Jarrod A.. And the article was published in Journal of the American Chemical Society in 2019. Recommanded Product: 2,4-Dichloropyrimidine The author mentioned the following in the article:
Despite recent clin. successes for irreversible drugs, potential toxicities mediated by unpredictable modification of off-target cysteines represents a major hurdle for expansion of covalent drug programs. Understanding the proteome-wide binding profile of covalent inhibitors can significantly accelerate their development; however, current mass spectrometry strategies typically do not provide a direct, amino acid level readout of covalent activity for complex, selective inhibitors. Here we report the development of CITe-Id, a novel chemoproteomic approach that employs covalent pharmacol. inhibitors as enrichment reagents in combination with an optimized proteomic platform to directly quantify dose-dependent binding at cysteine-thiols across the proteome. CITe-Id anal. of our irreversible CDK inhibitor THZ1 identified dose-dependent covalent modification of several unexpected kinases, including a previously unannotated cysteine (C840) on the understudied kinase PKN3. These data streamlined our development of JZ128 as a new selective covalent inhibitor of PKN3. Using JZ128 as a probe compound, we identified novel potential PKN3 substrates, thus offering an initial mol. view of PKN3 cellular activity. CITe-Id provides a powerful complement to current chemoproteomic platforms to characterize the selectivity of covalent inhibitors, identify new, pharmacol. addressable cysteine-thiols, and inform structure-based drug design programs. After reading the article, we found that the author used 2,4-Dichloropyrimidine(cas: 3934-20-1Recommanded Product: 2,4-Dichloropyrimidine)
2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Recommanded Product: 2,4-Dichloropyrimidine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia