MY-1B is a covalent inhibitor of the RNA Metltransferase NSUN2 (IC50: 1.3 μM). MY-1B stereoselectively ligands active-site cysteine residues (C271) of NSUN2. MY-1B can stereoselectively and covalently bind to PSME1, disrupting the proteasome regulatory complex and downregulating the presentation of specific MHC-I subtypes[1][2][3].
References:
[1]. Tao Y, et al. Chemical Proteomic Discovery of Isotype-Selective Covalent Inhibitors of the RNA Metltransferase NSUN2. Angew Chem Int Ed Engl. 2023 Dec 18;62(51):e202311924.
[2]. Tao Y, et al. Targeted Protein Degradation by Electrophilic PROTACs that Stereoselectively and Site-Specifically Engage DCAF1. J Am Chem Soc. 2022 Oct 12;144(40):18688-18699.
[3]. Ng BW, et al. Discovery of chemical probes that perturb protein complexes using size exclusion chromatograp and chemical proteomics. Mol Cell. 2023 May 18;83(10):1544-1546.