e3 enzyme

Pevonedistat (MLN4924) is a potent and selective NEDD8 activating enzyme (NAE) inhibitor (IC50=4.7 nM) with therapeutic potential for myelodysplastic syndromes (MDS) and antitumor activity.

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.

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.

Cbl-b-IN-12 (Example 10) is a CBL-B inhibitor with an IC50 of less than 100 nM [1].

Skp2 inhibitor 2 (14f) impedes the F-box protein S-phase kinase-associated protein 2 (Skp2), demonstrating an IC50 of 10.2 μM against Skp2-Cks1. This compound targets Skp2, a component of cullin-RING ligases that recruits and ubiquitinates substrates, playing roles in both proteolytic and non-proteolytic processes [1].

Cbl-b-IN-9 (Compound 300) is a potent inhibitor targeting casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl, with half-maximal inhibitory concentrations (IC50s) of 5.6 nM and 4.7 nM, respectively [1].

TRAF6 peptide TFA, a specific inhibitor of the TRAF6-p62 interaction, significantly inhibits NGF-dependent ubiquitination of TrkA. This peptide demonstrates promising research applications in various neurological disorders, including Alzheimer's disease (AD), Parkinson's, ALS, head trauma, epilepsy, and stroke [1].

Smurf1-IN-1, a selective E3 ubiquitin protein ligase 1 (SMURF1) inhibitor, exhibits oral activity with an IC50 of 92 nM and demonstrates considerable efficacy in a rat model of pulmonary hypertension [1].

Cbl-b-IN-11 (Compound 466) is an inhibitor of casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl, with half-maximal inhibitory concentrations (IC50s) of 6.4 nM and 6.1 nM, respectively [1].

Cbl-b-IN-7 (Compound 248) is an inhibitor of casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl, with half-maximal inhibitory concentrations (IC50s) of 6.7 nM and 5.2 nM, respectively [1].

Cbl-b-IN-8 (Compound 293) is an inhibitor of casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl, with half maximal inhibitory concentrations (IC50s) of 5.5 nM and 7.8 nM, respectively [1].

Cbl-b-IN-6 (Compound 246) is an inhibitor of casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl, with half-maximal inhibitory concentrations (IC50s) of 6.7 nM for Cbl-b and 5.2 nM for c-Cbl, respectively [1].

Cbl-b-IN-10 (Compound 463) is a potent inhibitor of both casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl, with half-maximal inhibitory concentrations (IC50s) of 6.0 nM and 3.5 nM, respectively [1].

Cbl-b-IN-13 (Example 520) is a potent Cbl-b inhibitor with an IC50 of less than 100 nM, capable of activating T-cells [1].

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

Cbl-b-IN-3 is a potent inhibitor of casitas b lineage lymphoma proto-oncogene-b (Cbl-b) (ic50 < 1 nM).

SCFSkp2-IN-2, a Skp2 inhibitor, exhibits a dissociation constant (K_D) of 28.77 μM. It demonstrates antitumor activities by inducing apoptosis in non-small cell lung cancer (NSCLC) cells.

MI-773 (SAR405838 (MI 773)) is an orally available MDM2 antagonist with Ki of 0.88 nM. Phase 1.

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]

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.

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

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

C25-140 is a small-molecule inhibitor of TRAF6-Ubc13.

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.