Table 1. Classification and summary of the 19S-associated DUB inhibitors.

Inhibitor	19S-associatedDUB/s	Substrate/s	First-reportedFunction	Related cell lines and tumor model	References
WP1130	UCHL5, USP14 (and USP9X, USP5)	MCL.1, p53	Induces tumor cells apoptosis through selectively inhibiting DUBs	MM1.S, Z138, HEK293T	[54]
IU1	USP14	Tau, TDP-43, cODC-EGFP	Accelerates the degradation of oxidized proteins and enhances resistance to oxidative stressin vitro	Primary mouse embryonic (MEFs), HEK293, HeLa	[83]
Tricyclic heterocyclics (IU2-6)	USP14	Tau	Accelerate the degradation of abnormal and/or misfolded proteins in cells	MEF	[86]
b-AP15	UCHL5, USP14	p53, ODC-1, CDKN1B, CDKN1A, Caspase-3, PARP	Inhibits tumor progression in vitro and in vivo	HCT-116, SCID mice with FaDu human tumor xenografts, C57BL/6J mice with syngenic LLC tumor, BALB/C mice with orthotopic breast carcinomas (4T1), Xenograft-derived CK18 in circulation	[87]
Azepan-4-ones	UCHL5, USP14	Bcl-2	Inhibit the refractory tumor	Multiple myeloma and other solid tumor malignancies like lung, prostate, colon, ovary, pancreas, breast, neck and head cancers	[93]
AC17	19S-associatedDUBs	NF-κB, p53, MDM2, p21	Suppresses the cell proliferation.	A549, BALB/C nude mice with A549 xenograft.	[94]
AuIII	UCHL1-C UCHL3-C UCHL5-C(C: a cysteine active site)	Caspase-7, PARP	Induces cell-cycle arrest, apoptosis and anti-angiogenic property in breast cancer cells	MCF-7, MDA-MB-231, HeLa, MIHA	[95]
CuPT	UCHL5, USP14	p21, p27, Bax, IκB-α, PARP, Caspase-3, Caspase-9, Caspase-8,	Selectively inhibits tumor growth in vivo and induces cytotoxicityin vitro and ex vivo	MCF-7, HepG2, U266, NCI-H929, GFPu-HEK293, Primary acute myeloid leukemia cells (AML), BALB/C nude mice with HepG2/NCI-H929 xenografts	[96]
Auranofin	UCHL5, USP14	c-Jun, p21, IκB-α, NF-κB, CHOP, Caspase-3,8,9,12, PARP	Inhibits tumor growth in vivo and induces cytotoxicityin vitro and ex vivo	MCF-7, HepG2, GFPu-HEK293, Primary acute myeloid leukemia cells (AML), BAB/C nude mice with HepG2/MCF-7 xenografts	[97]