Discovery of an Inhibitor of the Proteasome Subunit Rpn11 was written by Perez, Christian;Li, Jing;Parlati, Francesco;Rouffet, Matthieu;Ma, Yuyong;Mackinnon, Andrew L.;Chou, Tsui-Fen;Deshaies, Raymond J.;Cohen, Seth M.. And the article was included in Journal of Medicinal Chemistry in 2017.Computed Properties of C4H6N2S This article mentions the following:
The proteasome plays a crucial role in degradation of normal proteins that happen to be constitutively or inducibly unstable, and in this capacity it plays a regulatory role. Addnl., it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control function. Inhibitors of the proteasome have been validated in the treatment of multiple myeloma, with several FDA-approved therapeutics. Rpn11 is a Zn2+-dependent metallo-isopeptidase that hydrolyzes ubiquitin from tagged proteins that are trafficked to the proteasome for degradation A fragment-based drug discovery (FBDD) approach was utilized to identify fragments with activity against Rpn11. Screening of a library of metal-binding pharmacophores (MBPs) revealed that 8-thioquinoline (8TQ, IC50 value ∼2.5 μM) displayed strong inhibition of Rpn11. Further synthetic elaboration of 8TQ yielded a small mol. compound I (IC50 value ∼300 nM) that is a potent and selective inhibitor of Rpn11 that blocks proliferation of tumor cells in culture. In the experiment, the researchers used many compounds, for example, Thiazol-2-ylmethanamine (cas: 55661-33-1Computed Properties of C4H6N2S).
Thiazol-2-ylmethanamine (cas: 55661-33-1) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Computed Properties of C4H6N2S
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica