Xu, Guowei; Yang, Yaqing; Yang, Yanming; Song, Gao; Li, Shanshan; Zhang, Jiajun; Yang, Weimin; Wang, Liang-Liang; Weng, Zhiying; Zuo, Zhili published the artcile< The discovery, design and synthesis of potent agonists of adenylyl cyclase type 2 by virtual screening combining biological evaluation>, Safety of 4-Bromoisobenzofuran-1,3-dione, the main research area is adenylate cyclase agonist virtual screening cyclic adenosine monophosphate IL6; Adenylate cyclase; Agonist; Cyclic adenosine monophosphate; Interleukin-6; Virtual screening.
Adenylate cyclases (ACs), play a critical role in the conversion of ATP (ATP) into the second messenger cyclic adenosine monophosphate (cAMP). Studies have indicated that adenylyl cyclase type 2 (AC2) is potential drug target for many diseases, however, up to now, there is no AC2-selective agonist reported. In this research, docking-based virtual screening with the combination of cell-based biol. assays have been performed for discovering novel potent and selective AC2 agonists. Virtual screening disclosed a novel hit compound 8 as an AC2 agonist with EC50 value of 8.10μM on recombinant human hAC2 + HEK293 cells. The SAR (structure activity relationship) based on the derivatives of compound 8 was further explored on recombinant AC2 cells and compound 73 was found to be the most active agonist with the EC50 of 90 nM, which is 160-fold more potent than the reported agonist Forskolin and could selectively activate AC2 to inhibit the expression of Interleukin-6. The discovery of a new class of AC2-selective agonists would provide a novel chem. probe to study the physiol. function of AC2.
European Journal of Medicinal Chemistry published new progress about Drug screening (docking-based virtual screening). 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Safety of 4-Bromoisobenzofuran-1,3-dione.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary