6RK73 is a covalent irreversible and specific UCHL1 inhibitor with an IC50 of 0.23 µM. 6RK73 shows almost no inhibition of UCHL3 (IC50=236 µM). 6RK73 specifically inhibit UCHL1 activity in breast cancer.

A novel potent ubiquitin-specific protease USP1 inhibitor with IC50 of 78.1 nM, 5 times more potent than SJB2-043 in promoting ID1 degradation and cytoxicity in K562 cells.

BC-1471 is a selective, small-molecule deubiquitinase STAM-binding protein (STAMBP) inhibitor (IC50=0.33 uM) that interrupts STAMBP-Ub-NALP7 interaction.

P 217564 is a potent, selective, irreversible second generation inhibitor of USP7 with IC50 of 0.48 uM, with similar potency against USP47 and no significant activity aginst other DUBs.

LCAHA (LCA hydroxyamide) is a deubiquitinase USP2a inhibitor with IC50s of 9.7 μM and 3.7μM in Ub-AMC Assay and Di-Ub Assay, respectively. LCAHA destabilizes Cyclin D1 and induces G0/G1 arrest by inhibiting deubiquitinase USP2a.

USP30 inhibitor 11 is a selective and potent ubiquitin specific peptidase 30 (USP30) inhibitor with an IC50 of 0.01 µΜ, the example 83 extracted from patent WO2017009650A1. USP30 inhibitor 11 is used for the study of cancer and conditions involving mitochondrial dysfunction.

USP30 inhibitor 18 is a selective USP30 inhibitor with an IC50 of 0.02 μM. USP30 inhibitor 18 increases protein ubiquitination and accelerates mitophagy.

Vialinin A (Terrestrin A) is a p-terphenyl compound with antioxidant properties. Vialinin A is a potent inhibitor of TNF-α, USP4, USP5, and sentrin/SUMO-specific protease 1 (SENP1). Vialinin A (Terrestrin A) can be used for autoimmune diseases and cancer research.

FT3967385 is a novel USP30 inhibitor that recapitulates genetic loss of USP30 and sets the trigger for PINK1-PARKIN amplification of mitochondrial ubiquitylation.

USP5-IN-1 (compound 64), a potent deubiquitinase USP5 inhibitor, binds to the USP5 ZnF-UBD with a KD of 2.8 μM. USP5-IN-1 is selective over nine proteins containing structurally similar ZnF-UBD domains. USP5-IN-1 inhibits the USP5 catalytic cleavage of a di-ubiquitin substrate.

USP7i-1 is a potent, selective USP7 inhibitor..

EN523 (EN-523) is a small molecule covalent ligand EN523 that targets a non-catalytic allosteric cysteine C23 in the K48-ubiquitin-specific deubiquitinase OTUB1, OTUB1 recruiter component of DUBTAC NJH-2-057.Deubiquitinase-targeting chimeras (DUBTACs), heterobifunctional small molecules consisting of a deubiquitinase recruiter linked to a protein-targeting ligand, to stabilize the levels of specific proteins degraded in a ubiquitin-dependent manner.

iBAP-II (BAP1 inhibitor II) is a next-generation, specific small molecule inhibitor of BAP1 histone H2A deubiquitinase activity with IC50 of <0.1 ug/mL.iBAP-II displays higher affinity for BAP1 than the closest UCH family member, UCHL5, and other deubiquitinases, such as USP5, USP7, USP8, TNFAIP3-catalytic domain, USP2-catalytic domain, Otubain-1, and Ataxin3.Inhibition of BAP1 via iBAP-II reduces ASXL3 protein stability in small cell lung cancer cells, without significant changes to ASXL1 and ASXL2 protein levels.iBAP-II suppresses ASCL1 expression in NCI-H1963 cells, along with the mRNA levels involving a handful of known ASCL1 transcriptional targeted genes, such as GRP, DMPK, RNF183, SCN3A, MYCL, and CACNA1A.iBAP-II exhibited more potent cell viability inhibition activity on four different BAP1-WT SCLC cell lines than iBAP.iBAP-II (50 mg/kg/d) significantly delayed the disease progression in SCLC xenograft model.

IMP-1710 (IMP1710) is a potent, selective, covalent UCHL1 inhibitor with IC50 of 38 nM.IMP-1710 demonstrated exquisite selectivity in a cross-screening against 20 DUBs.IMP-1710 can profile activity of endogenous UCHL1 with excellent selectivity in cell types including endothelial cells (EA.hy926) and adenocarcinoma human alveolar basal epithelial cells (A549).IMP-1710 demonstrated >50% fibroblast–myofibroblast transition (FMT) inhibition (IC50=740 nM) in idiopathic pulmonary fibrosis (IPF), as well as αSMA inhibition.IMP-1710 is a powerful and selective probe to explore UCHL1 activity with potential application to substrate identification, mode of action studies, and cellular target profiling.

MT16-001 is a selective, covalent inhibitor of deubiquitinating enzyme UCHL1 with IC50 of 580 nM, no inhibitory effect against UCHL3 (IC50>30 uM).MT16-001 inhibits structurally unrelated DUB USP30 with similar potency.MT16-001 showed cytotoxicity in human embryonic kidney cells (HEK293) with EC50 of 730 nM, effectively engaged UCHL1 in cells with EC50 of 550 nM.MT16-001 showed excellent selectivity for UCHL1 across the UCH family: UCHL1, UCHL3, UCHL5 and BAP1.

MT16-205 (MT 16-205) is a potent, selective, covalent UCHL1 inhibitor with IC50 of 600 nM, no inhibition agianst UCHL3 (IC50>10 uM).MT16-205 inhibited both UCHL1 and the structurally unrelated DUB USP30 with similar potency.MT16-205 displayed cell proliferation cytotoxicity in human embryonic kidney cells (HEK293) with IC50 of 350 nM, MT16-205 effectively engaged UCHL1 in cells with IC50 of 830 nM.

NJH-2-075 is an alkyne-functionalized probe of EN523, retains binding to OTUB1 in vitro.

UCHL1 inhibitor 27 is a potent, selective, covalent UCHL1 inhibitor with IC50 of 90 nM.UCHL1 inhibitor 27 demonstrated exquisite selectivity in a cross-screening against 20 DUBs.UCHL1 inhibitor 27 demonstrated >50% fibroblast–myofibroblast transition (FMT) inhibition (IC50=100 nM) in idiopathic pulmonary fibrosis (IPF), as well as αSMA inhibition.UCHL1 inhibitor 27 is a powerful and selective probe to explore UCHL1 activity with potential application to substrate identification, mode of action studies, and cellular target profiling.

USP inhibitor 1 is an irreversible USP inhibitor with submicromolar IC50 of USP4 and its phylogenetic relative USP11, also functionally inhibits USP33, leading to CP110 instability and synergy with ATR inhibition in U2OS cells.

USP inhibitor 2 is a broad DUB inhibitor with IC50 of 0.04 and 0.21 uM for USP4 and USP11, also inhibits USP10/16/15/19 with submicromolar potency, forms a covalent adduct with USP11. USP inhibitor 2 does not inhibit USP5 (IC50>100 uM).

USP10 inhibitor Wu-5 (Wu-5) is a novel small molecule USP10 inhibitor inducing the degradation of FLT3-mutated protein, directly interacts and inactivates USP10, the deubiquitinase for FLT3-ITD in vitro (IC50=8.3 uM) and in FLT3-ITD-positive AML cells.Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC50 of 3.794, 5.056, and 8.386 uM, respectively.Wu-5 (1-10 μM) dose-dependently induced apoptosis of MV4-11, Molm13, and MV4-11R cells through the proteasome-mediated degradation of FLT3-ITD.Combined treatment of Wu-5 and crenolanib produced synergistic cell death in FLT3-ITD-positive cells via the reduction of both FLT3 and AMPKα proteins.

USP30 inhibitor Q14 peptide is a peptide derived from the transmembrane (TM) domain of USP30 that can target mitochondrial-anchored USP30 directly and increase mitophagy.