Computed Properties of C6H7Br2NIn 2017 ,《Discovery of Allosteric Inhibitors Targeting the Spliceosomal RNA Helicase Brr2》 was published in Journal of Medicinal Chemistry. The article was written by Iwatani-Yoshihara, Misa; Ito, Masahiro; Klein, Michael G.; Yamamoto, Takeshi; Yonemori, Kazuko; Tanaka, Toshio; Miwa, Masanori; Morishita, Daisuke; Endo, Satoshi; Tjhen, Richard; Qin, Ling; Nakanishi, Atsushi; Maezaki, Hironobu; Kawamoto, Tomohiro. The article contains the following contents:
Brr2 is an RNA helicase belonging to the Ski2-like subfamily and an essential component of spliceosome. Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step for spliceosomal activation. An HTS campaign using an RNA-dependent ATPase assay and initial SAR study identified two different Brr2 inhibitors, 3 (I) and 12 (II). Cocrystal structures revealed 3 binds to an unexpected allosteric site between the C-terminal and the N-terminal helicase cassettes, while 12 binds an RNA-binding site inside the N-terminal cassette. Selectivity profiling indicated the allosteric inhibitor 3 is more Brr2-selective than the RNA site binder 12. Chem. optimization of 3 using SBDD culminated in the discovery of the potent and selective Brr2 inhibitor 9 (III) with helicase inhibitory activity. The authors’ findings demonstrate an effective strategy to explore selective inhibitors for helicases, and 9 could be a promising starting point for exploring mol. probes to elucidate biol. functions and the therapeutic relevance of Brr2. In the experiment, the researchers used 2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8Computed Properties of C6H7Br2N)
2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8) belongs to pyridine. Pyridine and pyridine-derived structures are privileged pharmacophores in medicinal chemistry and an essential functionality for organic chemists. As the prototypical π-deficient heterocycle, pyridine illustrates distinctive chemistry as both substrate and reagent. Computed Properties of C6H7Br2N