Discovery of Potent and Selective Inhibitors against Protein-Derived Electrophilic Cofactors was written by Wang, Xie;Lin, Zongtao;Bustin, Katelyn A.;McKnight, Nate R.;Parsons, William H.;Matthews, Megan L.. And the article was included in Journal of the American Chemical Society in 2022.Safety of (1H-Imidazol-2-yl)methanamine dihydrochloride This article mentions the following:
Electrophilic cofactors are widely distributed in nature and play important roles in many physiol. and disease processes, yet they have remained blind spots in traditional activity-based protein profiling (ABPP) approaches that target nucleophiles. More recently, reverse-polarity (RP)-ABPP using hydrazine probes identified an electrophilic N-terminal glyoxylyl (Glox) group for the first time in secernin-3 (SCRN3). The biol. function(s) of both the protein and Glox as a cofactor has not yet been pharmacol. validated because of the lack of selective inhibitors that could disrupt and therefore identify its activity. Here, we present the first platform for analyzing the reactivity and selectivity of an expanded nucleophilic probe library toward main-chain carbonyl cofactors such as Glox and pyruvoyl (Pyvl) groups. We first applied the library proteome-wide to profile and confirm engagement with various electrophilic protein targets, including secernin-2 (SCRN2), shown here also to possess a Glox group. A broadly reactive indole ethylhydrazine probe was used for a competitive in vitro RP-ABPP assay to screen for selective inhibitors against such cofactors from a set of com. available nucleophilic fragments. Using Glox-containing SCRN proteins as a case study, naphthyl hydrazine was identified as a potent and selective SCRN3 inhibitor, showing complete inhibition in cell lysates with no significant cross-reactivity detected for other enzymes. Moving forward, this platform provides the fundamental basis for the development of selective Glox inhibitors and represents a starting point to advance small mols. that modulate electrophile-dependent function. In the experiment, the researchers used many compounds, for example, (1H-Imidazol-2-yl)methanamine dihydrochloride (cas: 22600-77-7Safety of (1H-Imidazol-2-yl)methanamine dihydrochloride).
(1H-Imidazol-2-yl)methanamine dihydrochloride (cas: 22600-77-7) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.Safety of (1H-Imidazol-2-yl)methanamine dihydrochloride
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem