ubiquitin ligase

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.

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.

E3 ligase Ligand 23 is a cereblon binding agent that degrades Ikaros or Aiolos via the ubiquitin proteasome.

FKBP12 PROTAC dTAG-7 (dTAG-7) is a heterobifunctional compound that selectively degrades the BET bromodomain transcriptional co-activator BRD4 by linking BET bromodomains to the E3 ubiquitin ligase CRBN. It also functions as a degrader of FKBP12F36V when FKBP12F36V is expressed in-frame with a targeted protein.

VH032 commonly used as a precursor to a PROTAC that hijacks VHL as the E3 ubiquitin ligase component.VH032 is a VHL HIF-1α interaction inhibitor with a KdPROTACs, which can recruit von Hippel-Lindau (VHL) proteins as a ligand of VHL.

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]

alphaSYN-IN-NAB2, a neuron-protective agent, is a protein encoded by the NAB2 gene. NAB2 effectively and selectively protects a variety of cells from alpha-SYN toxicity. NAB2 promotes endosomal transport dependent on E3 ubiquitin ligase Rsp5 Nedd4. NAB2 identifies a viable molecular node in alpha-SYN biology that corrects multiple aspects of its underlying pathology, including dysfunctional endosomes and endoplasmic reticulum to Golgi vesicles transport. NAB2 is involved in cellular processes such as cell differentiation, apoptosis and stress response, and can be used to study cancer, neurodevelopment and neuronal activity.

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

Lenalidomide (CC-5013) is an immunomodulator with oral activity. Lenalidomide is a ligand for the ubiquitin E3 ligase cereblon (CRBN), which selectively ubiquitinates and degrades two lymphoid transcription factors, IKZF1 and IKZF3, via the CRBN-CRL4 ubiquitin ligase, and is commonly used in the synthesis of PROTAC products.

Pomalidomide (CC-4047) is an anti-angiogenic and immunomodulatory agent. Pomalidomide is a ligand for the ubiquitin E3 ligase cereblon (CRBN) and is commonly used in the synthesis of PROTAC products.

Lenalidomide-Br (Compound 41), a derivative of Lenalidomide, acts as a ligand for cereblon (CRBN) - an E3 ubiquitin ligase involved in protein recruitment. This compound can be conjugated to a protein ligand via a linker to create PROTACs, such as the PROTAC STAT3 degrader SD-36.

Nrf2 degrader 30 is a small molecule PROTAC that inhibits the degradation of Nrf2, thereby enhancing its activity. Nrf2 is a key transcription factor that regulates cellular antioxidant responses and various protective mechanisms. The activity of Nrf2 is primarily regulated by its interaction with Keap1, which serves as an E3 ubiquitin ligase complex adapter to promote Nrf2 ubiquitination and proteasomal degradation。

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.

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

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.

2-D08 is a synthetic flavone that inhibits sumoylation, also inhibits Axl with an IC50 of 0.49 nM.2-D08 showed anti-aggregatory and neuroprotective effect.

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

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

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

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

dCBP-1 is a chemical degrader of p300 CBP. dCBP-1 hijacks the E3 ubiquitin ligase CRBN for selective degradation of p300 CBP. Degradation of p300 CBP by dCBP-1 leads to effective multiple myeloma cell killing.