E3 ligating enzyme

Mezigdomide (CC-92480) is a potent, novel, selective and active cereblon E3 ubiquitin ligase modulator (CELMoD) that acts as a molecular glue. Mezigdomide has anti-myeloma activity. [1]

Indole-3-carbinol (I3C), a naturally occurring, orally available cleavage product of the glucosinolate glucobrassicanin, inhibits NF-κB and IκBα kinase activation.

YH239-EE, the ethyl ester of YH239, is a potent p53-MDM2 antagonist and an apoptosis inducer.

Nutlin-3b ((+)-Nutlin-3) is a p53/MDM2 antagonist or inhibitor (IC50: 13.6 μM), 150-fold less potent (+)-enantiomer of Nutlin-3 as in comparison with opposite (-)-enantiomer Nutlin-3a.

MD-224 is a highly potent and efficacious MDM2 degrader based on the proteolysistargeting chimera (PROTAC) concept,and as a new class of anticancer agent.

NSC232003 is a highly potent and cell-permeable inhibitor of [UHRF1].

Ubiquitination-IN-1 is an inhibitor of ubiquitination and Cksl-Skp2 protein-protein interaction (IC50: 0.17 μM).

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

BH3I-1 (BHI1) is a Bcl-2 antagonist.

ML-792 is a specific small ubiquitin-like modifier activating enzyme (SUMO) inhibitor. ML-792 selectively inhibits SAE/SUMO1 and SAE/SUMO2 with IC50 of 3 and 11 nM.

PYZD-4409 is a selective UBA1 inhibitor with an IC50 of 20 μM. PYZD-4409 induces cell death in malignant cells and is preferentially cytotoxic to malignant cells over normal hematopoietic cells.

SJ-172550 is a small molecule inhibitor of MDMX (EC50: 5 μM).

SMIP004 is an SKP2 E3 ligase inhibitor. SMIP004 is a cancer cell-selective apoptosis inducer of human prostate cancer cells.

TAK-243 (MLN7243) is a selective inhibitor of the ubiquitin-activating enzyme UAE (IC50=1 nM), blocking ubiquitin binding and disrupting both mono-ubiquitin signaling and overall protein ubiquitination. TAK-243 exhibits antitumor activity and promotes apoptosis.

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.

Serdemetan (JNJ-26854165) is an orally bioavailable HDM2 antagonist with potential antineoplastic activity.

SMER3 is an inhibitor of the Skp1-Cullin-F-box (SCF)(Met30) ubiquitin ligase, a member of the SCF E3-ligase family, which regulates diverse cellular processes including transcription, cell-cycle control and immune response.

Heclin is an inhibitor of HECT E3 ubiquitin ligase that acts by inhibiting Smurf2, Nedd4, and WWP1 with IC50 values of 6.8, 6.3, and 6.9 μM, respectively.

GS143 is a selective IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. It suppresses NF-κB activation and transcription of target genes without inhibiting proteasome activity. GS143 has anti-asthm[atic] properties.

PRT4165 (NSC600157) is a potent PRC1-mediated H2A ubiquitylation inhibitor.

SZL P1-41, a skp2 inhibitor, can prevent assembly of Skp2-Skp1 complexes. It selectively suppresses Skp2 SCF E3 ligase activity but exhibits no effect on the activity of other SCF complexes. It also inhibits Skp2-mediated p27 and Akt ubiquitination in vivo and in vitro. It suppresses the survival of Y cells and Y stem cells by triggering cell senescence and inhibiting glycolysis. It exhibits antitumor effects in multiple animal models and Y cell lines.

RO8994 is a highly effective and specific inhibitor of spiroindolinone small-molecule MDM2, with IC50 of 20 nM (MTT proliferation assays) and 5 nM (HTRF binding assays).

Avadomide (CC 122) is an orally available pleiotropic pathway modulator with potential antineoplastic activity.

MX69 is the MDM2/XIAP inhibitor, blocking the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation.