Table 2.

Selective isopeptidase inhibitors

Compound	Isopeptidase	Activity	Specificity	Mechanism	Cell effects	Ref.
O-acyl oxime derivatives of isatins	UCH-L1	IC50 0.80-0.94 μM	IC50 for UCH-L3 17-25 μM	Reversible competitive active site directed	Promote proliferation of H1299 and SHSY5Y cells.	[64]
3-Amino-2-keto-7H-thieno[2,3-b] pyridin-6-one derivatives	UCH-L1	Ki 2.8 μM	Not active for UCHL3, and various cystein proteases	Uncompetitive substrate/enzyme complex directed	Not reported	[68]
N,N0-4,40- Biphenyldiylbis(4 Ethylbenzenesulfo namide)	UCH-L1	IC50 15 μM	Not reported	Active site directed	Not reported	[69]
2-methyl- N -[1-(2-naphthyl) ethyl] benzamide derivative	PLpro	IC50 0.6 μM	IC50>100 for various DUBs and cystein proteases	Reversible competitive directed active site	Antiviral activity in Vero E6 cells, EC50=10-15 μM	[78]
Cyanoidenopyrazine derivative	USP7	IC50 0.42 μM	Partial specificity	Reversible, non competitive	Induction of p53 activity, inhibition of cell proliferation and induction of p53 dep. apoptosis	[74]
Not reported HBX 28,231 HBX 28,218	USP7	Low μmolar range	No activity against various DUBs and cystein proteases.	Not reported	Induction of p53 activity, inhibition of cell proliferation and induction of p53 dep. Apoptosis.	[30][75]
9-Oxo-9h-indeno [1,2-b]pyrazine-2,3-dicarbonitrile analogues	USP8	IC50 0.98-0.56 μM	No activity against various DUBs and cystein proteases, partial activity against UCH-L3.	Not reported	Affected viability of cancer cells lines HTC116 and PC-3 IC50 0.5-1.5 μM	[77]