e1/e2/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.

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

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

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.

ZM223 is an inhibitor of NEDD8 activating enzyme (NAE).

BI8626 is a ubiquitin ligase HUWE1 inhibitor with protective effects against spontaneous desiccation syndrome in NOD/ShiLtj mice.BI8626 inhibits intracellular cholesterol and decreases the expression of phosphorylated ZAP-70, CD25, and other activation markers, and inhibits the proliferation of CD4 T-cells.

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

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.

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.

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.

Hinokiflavone, a novel modulator of pre-mRNA splicing activity both in vitro and in cellulo, inhibits the assembly of the spliceosome, particularly blocking the formation of the B complex. Additionally, it acts as a SUMO protease inhibitor by impeding the activity of sentrin-specific protease 1 (SENP1). Hinokiflavone also demonstrates significant cytotoxicity, including the inhibition of MMP-9.

COH000 is a covalent and irreversible inhibitor of small ubiquitin-like modifier (SUMO)-activating enzyme and inhibited SUMOylation (IC50: ~ 0.2 μM in vitro).

Siremadlin (NVP-HDM 201) is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor.

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.

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

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.

Ginkgolic Acid (Romanicardic acid) C15:1 represses curli genes and prophage genes in EHEC.