Table 3.

Repurposed E3 inhibitors (3A) and DTC-based proteasome inhibitors (3B).

	Compounds	Targets	Chemical Structure	Inhibitory activity	Ref.
3A	Thalidomide	CRBN		Stabilizes CRBN by inhibiting its autoubiquitination through direct binding, inducing CRBN-mediated ubiquitination and degradation of target proteins	[214]
	Lenalidomide	CRBN		Same as Thalidomide	[217]
	ARV-825	CRBN, BRD4		Promotes the CRBN-dependent degradation of BRD4 through dual interactions with both molecules.	[222]
	Lovastatin	Skp2		Decreases the expression of Skp2 and results in the inhibition of Skp2-mediated ubiquitination and degradation of p27 and p21, leading to cell cycle arrest and apoptosis	[231,232]
	Clomipramine	ITCH		Interferes with the HECT Ub transthiolation activity of ITCH in an irreversible manner	[250]
	JS-K	Mdm2		Inhibits Mdm2 E3 ultimately accumulating p53 concentrations leading to inhibition of the ubiquitin proteasome pathway; Also, able to generate DNA damage and increase p53 concentrations	[264]
	Suramin	CRL		Targets CRL-mediated K48 polyubiquitination and inhibits Cullin-RING E3 ubiquitin ligase	[267]
3B	DSF	20S		DSF-Cu complex: Inhibition of the CT-L activity of the purified 20S proteasome (IC50=~7.5 μM); > 95 % inhibition of proteasomal CT-L activity in MDA-MB-231 cancer cells at 20 μM	[272]
	DDTC	20S		DDTC/Cu complex: 35 % inhibition of the CT-L activity of purified 20S proteasome at 50 μM; > 90 % inhibition of cellular 26S proteasome at 20 μM in intact cells	[275]
		19S DUB		AgDT: inhibition of the DUB activities of UCHL5 and USP14 at 0.08 μM.	[283]
		NPL4		CuET: Inhibition of p97-segregase–dependent protein degradation via interacting with NPL4 and inducing NPL4 immobilization and aggregation.	[290]
	PDTC	20S		Inhibition of the CT-L activity of purified 20S proteasome with IC50 values of 13.8 μM for PDTC/Zn and 5.3 μM for PDTC/Cu	[287]
	Au(DMDT)Br2,	20S		Inhibition of the CT-L activity of the purified 20S proteasome (IC50 = 7.4 μM) and 26S proteasome in intact MDA-MB-231 cancer cells (10–20 μM)	[144]
	AuBr2(ESDT)	20S		Inhibition the CT-L activity of the purified 20S proteasome (IC50 = 1.13 μM) and 26S proteasome in intact MDA-MB-231 cancer cells	[288]
	[Au(ESDT)]2	20S		Inhibition of the CT-L activity of the purified 20S proteasome (IC50 = 17.72 μM) and 26S proteasome in intact MDA-MB-231 cancer cells	[288]