Recently I am researching about CRYSTAL-STRUCTURE; 20S PROTEASOME; ALPHA; EXPRESSION; BORTEZOMIB; SUBSTRATE; DOCKING, Saw an article supported by the DFGGerman Research Foundation (DFG)European Commission [GRK1657]. Formula: C5H4N2O2. Published in WILEY-V C H VERLAG GMBH in WEINHEIM ,Authors: Stubba, D; Bensinger, D; Steinbacher, J; Proskurjakov, L; Gomez, AS; Schmidt, U; Roth, S; Schmitz, K; Schmidt, B. The CAS is 98-97-5. Through research, I have a further understanding and discovery of Pyrazine-2-carboxylic acid
The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported alpha-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted alpha-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome beta 5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1 ‘ by a 3-phenoxy group to increase beta 5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the alpha-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.
Formula: C5H4N2O2. Bye, fridends, I hope you can learn more about C5H4N2O2, If you have any questions, you can browse other blog as well. See you lster.
Reference:
Patent; Chevron Research Company; US4732894; (1988); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem