Table 7.

List of some inhibitors reported to target USPs and their cellular effects.

USP	Inhibitor	Effects	Refs.
USP1	Pimozide	Increases ubiquitination levels of PCNA and FANCD2 and inhibits growth and viability in U2OS and MCF10A cells	[171]
	ML323	High specificity for USP1/UAF1; increases ubiquitination levels of PCNA and FANCD2 in HEK293T and H596 cells	[172]
		Inhibits (synergistic effect with cisplatin) proliferation in H596 and U2OS cells	[173]
		Inhibits migration/invasion ability of MCF7, MDA-MB231 and 4T1 cells; suppresses lung metastasis in mice harboring 4T1 tumors	[174]
	SJB2-043	Induces apoptosis of K562 cells	[175]
	SJB3-019A	A potent USP1 inhibitor, five times more potent than SJB2-043 in inducing apoptosis in K562 cells
	C527	Degrades ID1 in human U2OS cells and increases the levels of Ub-FANCD2 and Ub-FANCI in HeLa cells
USP2	AM146	Provokes cell cycle arrest and apoptosis in MDA-MB231 and MDA-MB468 cells	[176]
	RA-9
	RA-14
	ML364	Increases cyclin D1 degradation, blocks G1/S transition and inhibits cellular proliferation in colorectal cancer HCT116 and Mino (mantle cell lymphoma) cells	[177]
USP4	Vialinin A	Inhibits the enzymatic activity of USP4, USP5 and UCHL1	[178]
USP5	WP1130	Induces ubiquitination of p53 and Mcl-1 in Z138 cells	[179]
	Vialinin A	Inhibits the enzymatic activity of USP4, USP5 and UCHL1	[178]
	EOAI3402143 (G9)	Suppresses p53 and FAS levels in A375 cells; suppresses melanoma growth in mice harboring A375 tumors	[180]
	RA-9	Provokes cell cycle arrest and apoptosis in MDA-MB231 and MDA-MB468 cells	[176]
	RA-14
USP7	HBx19818	Stabilizes p53 and promotes G1 arrest and apoptosis in HCT116 cells	[181]
	HBx28258	Reduces HCT116 cell proliferation, induces caspase activity and PARP cleavage and arrests HCT116 cancer cells in G1 phase
	HBx41108	Stabilizes and activates p53, inhibits HTC116 cell growth and induces p53-dependent apoptosis	[182]
	P5091	Induces apoptosis in MM.1S cells	[183]
	P22077	Predominantly inhibits USP7, thus regulating the apoptotic pathway of p53; suppresses neuroblastoma growth in mice harboring IMR32 tumors	[184,185,186]
	FT671	Increases p53 protein levels in HCT116 and U2OS cells and stabilizes p53 in MM.1S cells; suppresses multiple myeloma growth in mice harboring MM.1S tumors	[187]
	XL188	Promotes the accumulation of p53 and p21 in MCF7 and MM.1S cells	[188]
USP8	RA-9	Decreases viability of HeLa, SiHa, CaSki, TOV21G1, SKOV3, ES-2, MDA-MB231, MDA-MB435A and MDA-MB468 cells	[176]
		Induces apoptosis in ES-2 cells; suppresses ovarian cancer growth; and increases overall survival in mice harboring ES-2 tumors	[189]
	RA-14	Decreases viability of HeLa, SiHa, CaSki, TOV21G1, SKOV3, ES-2, MDA-MB231, MDA-MB435A and MDA-MB468 cells	[176]
	AM146
USP9x	WP1130	Reduces levels of Mcl-1 protein and stimulates apoptosis in K562 cells	[190]
	EOAI3402143 (G9)	Induces apoptosis in MV4 11 and K562 cells
		Reduces Mcl-1 levels and increases p53 levels and apoptosis in MM.1S cells; decreases tumoral growth in mice bearing tumor xenografts from MM.1S cells	[191]
USP10	P22077	Degrades FLT3, leading to death of HEK293T cells	[192]
	HBx19818
	Spautin1	Induces degradation of the PI3K3C3 complex and leads to apoptosis of K562 cells	[193]
USP11	Mitoxantrone	Increases apoptosis in PL5 cells	[194]
USP13	Spautin1	Induces degradation of the PI3K3C3 complex and leads to apoptosis of K562 cells	[193]
USP14	b-AP15	Inhibits cell growth and overcomes bortezomib resistance in MM.1S cells; anti-cancerous effect against solid tumors and multiple myeloma in vivo	[195,196]
	VLX1570	Analogue of b-AP15 that induces toxicity and apoptosis in OPM2, KMS11, BCWM3 and RPCI-WM1 cells	[197,198,199]
	WP1130	Inhibits the activity of several DUBs such as USP5, UCH-L1, USP9x, USP14, and UCH37	[179]
	IU1	Induced cell cycle arrest and apoptosis in MDA-MB153 and MDA-MB231 cells and inhibited cell proliferation in LNCaP cells; decreases (synergistic effect with enzalutamide) tumoral growth in mice bearing tumor xenografts from MCF7 cells	[200,201,202]
USP24	EOAI3402143 (G9)	Reduces Mcl-1 levels and increases p53 levels and apoptosis in MM.1S cells; decreases tumoral growth in mice bearing tumor xenografts from MM.1S cells	[191]