KSC-34, a covalent modifier of protein disulfide isomerase A1 (PDIA1), is also a selective and potent a-site inhibitor of PDIA1 with an IC50 of 3.5 μM. KSC-34 displays a 30-fold selectivity for a domain over a′ domain and displays high selectivity for PDIA1 in complex proteomes with minimal engagement of other members of the PDI family[1].
KSC-34 is selective for PDIA1 over other members of the PDI family, and other cellular cysteine-containing proteins. KSC-34 contains a (4-phenylbutyl)methylamine diversity element for optimized binding to the active site of the a domain of PDIA1 with a chloroacetamide electrophile for covalent modification of C53 on PDIA1[1].
[1]. Cole KS, et al. Characterization of an A-Site Selective Protein Disulfide Isomerase A1 Inhibitor. Biochemistry. 2018;57(13):2035-2043.