Nutlin-3 is an MDM2 antagonist that inhibits MDM2-p53 interaction (Ki=90 nM) and activates p53. Nutlin-3 binds preferentially to the p53-binding pocket of MDM2, leading to stabilization of p53 and activation of the p53 pathway. Nutlin-3 has antitumor activity.

Idasanutlin (Ro 5503781) (RG-7388) is an effective and specific p53-MDM2 inhibitor (IC50: 6 nM).

NSC-697923 (2-[(4-methylphenyl)sulfonyl]-5-nitrofuran), a potent inhibitor of UBE2N (ubiquitin-conjugating enzyme E2 N, Ubc13), exhibits its role in inducing cell death in neuroblastoma (NB) cells through two distinct mechanisms. In p53 wild-type NB cells, NSC-697923 promotes the nuclear importation of p53, thereby triggering cell death. Meanwhile, in p53 mutant NB cells, NSC-697923 activates the JNK-mediated apoptotic pathway, leading to cell death. Additionally, NSC-697923 inhibits DNA damage and NF-κB signaling, further contributing to its antitumor activity.

PYR-41 is the first cell-permeable inhibitor of ubiquitin-activating enzyme E1, with no activity at E2.

RG7112 (RO5045337) (RO5045337) is an orally bioavailable and selective p53-MDM2 inhibitor.

Navtemadlin (AMG232) is a potent, selective and orally available inhibitor of p53-MDM2 interaction (IC50: 0.6 nM). It binds to MDM2 with a Kd of 0.045 nM.

BC-1382 is a potent ubiquitin E3 ligase HECTD2 inhibitor that specifically disrupts the HECTD2/PIAS1 interaction(IC50 of 5 nM).

WS-383 is a selective, potent and reversible DCN1-UBC12 interaction inhibitor(IC50 of 11 nM).