Table 2.

The agonists of E3 ligases.

Drug Class	Agent	Mechanism	Tumor Types	Phase	Reference
E3 ligase agonists
Cereblon (CRBN) agonists	Lenalidomide, Thalidomide, Pomalidomide	Modulation of the substrate specificity of the CRL4-CRBN E3 ubiquitin ligase, induces the ubiquitination of IKZF1 and IKZF3	Multiple myeloma, diffuse large B-cell lymphoma	FDA approved (Phase 4)	[236,237,238,239]
	CC-90009	Promotes binding of cereblon to GSPT1, leading to enhanced ubiquitination and subsequent degradation	AML, leukemia, myelodysplastic syndromes	1, 2	[240,241]
	CC-122 (Avadomide), CC-220 (Iberdomide)	Cereblon E3 ligase modulators (CELMoDs)	AML, multiple myeloma, diffuse large B-cell lymphoma (DLBCL), advanced solid tumors, non-Hodgkin’s lymphoma (NHL), melanoma	1, 2	[239]
β-TrCP agonists	NRX-252114, NRX-252262, NRX-1532, NRX-1933, NRX-2663, NRX-103094, RX-103095	Promotes the interaction of β-TrCP with β-catenin	N/A	Preclinical	[242]
DCAF15 agonists	Indisulam(E7070), Tasisulam, CQS	Promotes the binding of Rbm39 to DCAF15	Metastatic breast cancer, gastric cancer, leukemia, melanoma (skin), solid tumor, kidney neoplasms, adenocarcinoma, CRC	1, 2	[243]
TIR1 agonists	Hormone auxin	Binds to SCF F-box subunit TIR1 and promotes the interaction between TIR1 and its substrate	N/A	Preclinical	[244]
NPR agonists	Aalicylic acid (SA)	Regulates the effect of CRL3-NPR	N/A	Preclinical	[244,245]
COI1 agonists	Jasmonic acid (JA)	Facilitates the molecular association between SCF-COI1 ligase and its substrates	N/A	Preclinical	[244]
N/A: not applicable