UCHL1 Inhibitor

GK13S is a deubiquitinase UCHL1 ligand and inhibitor. GK13S inhibits recombinant and cellular UCHL1. GK13S reduces levels of monoubiquitin in human glioblastoma cells. GK13S is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

8RK64 is a UCHL1 inhibitor that covalently binds the active-site cysteine residue to form an isothiourea adduct, with selectivity over UCHL3, UCHL5, and other cysteine DUBs. 8RK64 inhibits human UCHL1 with an IC₅₀ of 0.32 μM. 8RK64 is an azide-containing precursor usable as a two-step activity-based probe via click chemistry. 8RK64 can be used for the research of Parkinson's disease.

UCHL1-IN-1 (Compound 46) is an inhibitor for Ubiquitin C-terminal Hydrolase L1 (UCHL1), with an IC₅₀ of 5.1 μM. UCHL1-IN-1 can be used for cancer research.

Z-VAE (OMe)-FMK is a selective inhibitor of UCHL1, with better selectivity over UCHL3 and UCHL5. Z-VAE (OMe)-FMK binds to the active site cleft, covalently modifies the active site cysteine C90 to form a thioether bond, binds to inactive UCHL1 with a misaligned catalytic triad, and acts via a two-step addition-folding/migration/displacement mechanism. Z-VAE (OMe)-FMK stabilizes interactions through hydrogen bonding with oxyanion hole residues and van der Waals interactions with surrounding residues. Z-VAE (OMe)-FMK can be used in research related to colorectal cancer, lung cancer, pancreatic cancer, and Alzheimer's disease.