Yu, Yancheng published the artcileInsight into the binding mode of HIF-2 agonists through molecular dynamic simulations and biological validation, Recommanded Product: Phthalonitrile, the main research area is hypoxia inducible factor agonist mol dynamic simulation; Agonist; Binding mode; HIF-2; Molecular dynamic simulations.
Hypoxia-inducible factor-2 (HIF-2), a heterodimeric transcriptional protein consisting of HIF-2α and aryl hydrocarbon receptor nuclear translocator (ARNT) subunits, has a broad transcriptional profile that plays a vital role in human oxygen metabolism M1001, a HIF-2 agonist identified by high-throughput screening (HTS), is capable of altering the conformation of Tyr281 of the HIF-2α PAS-B domain and enhancing the affinity of HIF-2α and ARNT for transcriptional activation. M1002, an analog of M1001, shows improved efficacy than M1001. However, the cocrystal structure of M1001 and HIF-2 has some defects in revealing the agonist binding mode due to the relatively low resolution, while the binding mode of M1002 remained unexplored. To in-depth understand agonist binding profiles, herein, the mol. dynamic (MD) simulations was applied to construct a stable agonist-protein model, and a possible binding mode was proposed through the anal. of the binding free energy and hydrogen bonding of the simulation results. Nine compounds were then synthesized and evaluated to verify the proposed binding mode. Among them, compound 10 manifested improved agonistic activity and reduced toxicity compared to M1002. This study provides deep insight into the binding mode of such HIF-2 agonists, which would be useful for designing novel agonists for HIF-2.
European Journal of Medicinal Chemistry published new progress about Bond length. 91-15-6 belongs to class nitriles-buliding-blocks, name is Phthalonitrile, and the molecular formula is C8H4N2, Recommanded Product: Phthalonitrile.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts