ubiquitination

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

dCeMM3 (2-(1H-benzimidazol-2-ylsulfanyl)-N-(5-chloropyridin-2-yl)acetamide) is a glue degrader. dCeMM3 prompts an interaction of CDK12-cyclin K with a CRL4B ligase complex, result in inducing ubiquitination and degradation of cyclin K.

PR-619 (2,6-Diamino-3,5-dithiocyanopyridine) is a DUB inhibitor that inhibits USP2/4/5/7/8 (EC50=7.2/3.93/8.61/6.86/4.9 μM). PR-619 induces endoplasmic reticulum stress and activates autophagy.

CYM5442 is an S1P agonist, targeting to Sphingosine.

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.

Lanosterol (3β-Hydroxy-8,24-lanostadiene) is a tetracyclic triterpenoid which is the compound from which all steroids are derived.

TCID (UCH-L3 Inhibitor)(IC50=0.6 μM) is a DUB inhibitor of ubiquitin C-terminal hydrolase L3. It has the 125-fold selectivity to L1.

MID-1 is an inhibitor of MG53-IRS-1 (Mitsugumin 53-Insulin Receptor Substrate-1) interaction. It disrupts molecular association of MG53 with IRS-1 and abolishes MG53-induced IRS-1 ubiquitination and degradation in skeletal muscle, leading to elevated IRS-1 expression level and increased insulin signaling and glucose uptake

ICCB-19 hydrochloride (ICCB-19 HCl) is an inhibitor of TRADD (TNFRSF1A Associated Via Death Domain). It binds to a pocket on the N-terminal TRAF2-binding domain of TRADD (TRADD-N), which interacts with the C-terminal domain (TRADD-C) and TRAF2 to modulate the ubiquitination of RIPK1 and beclin 1.

CC0651 is a highly selective allosteric inhibitor of human Cdc34 ubiquitin-conjugating enzyme (UCE), inhibiting p27 Kip1 ubiquitination (IC50=1.72 μM) by blocking ubiquitin transfer to substrates, for use in cancer research.

SP 141 is a MDM2 inhibitor.SP-141 promotes MDM2 auto-ubiquitination and degradation, with anticancer activity.

Ubiquitination-IN-2 is a potent inhibitor of E1-E2 protein−protein interactions (PPI), exhibiting inhibitory activity with a dissociation constant (Kd) of 0.72 μM for the ubiquitin E1 (Uba1) enzyme. By blocking the transfer of ubiquitin from E1 to E2, Ubiquitination-IN-2 serves as a valuable tool in cancer research [1].

20-HETE belongs to endogenous metabolites (natural products) and is a protein kinase C (PKC) pathway activator that promotes ACSL4 ubiquitination and degradation through upregulation of FBXO10, possessing regulatory properties on cell proliferation and migration. This compound is used in research related to prostate tumors and cardiac hypertrophy.

USP30 inhibitor 18 is a selective USP30 inhibitor with an IC50 of 0.02 μM. USP30 inhibitor 18 increases protein ubiquitination and accelerates mitophagy[1]. [1]. Arthur F Kluge, et al. Novel highly selective inhibitors of ubiquitin specific protease 30 (USP30) accelerate mitophagy. Bioorg Med Chem Lett. 2018 Aug 15;28(15):2655-2659.

C004019 belongs to PROTACs and is a tau protein-targeted degrader (via recruitment of VHL E3 ligase) with blood-brain barrier permeability and selective tau degradation capability. This compound significantly reduces tau levels and improves cognitive function, and is used in research on Alzheimer's disease and related tauopathies.

HM90822 is a novel synthetic apoptotic protein (IAP) antagonist that induces apoptosis in human pancreatic cancer cells through proteasome-dependent degradation of IAPs containing the BIR2/3 structural domain.HM90822 inhibits the expression of XIAP and cIAP1/2 proteins in HM822-sensitive Panc-1 and BxPC-3 cells, induces ubiquitylation of IAPs and promotes induces IAP ubiquitination and promotes proteasome-dependent IAP degradation.

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。

Fluconazole-PEG6-XMU-MP-9 is a PEG-linked conjugate of fluconazole and XMU-MP-9. Fluconazole is a triazole antifungal agent, while XMU-MP-9 enhances the interaction between Nedd4-1 and K-Ras, promoting the ubiquitination and degradation of multiple K-Ras mutants.

Fluconazole-C15-XMU-MP-9 is a fluconazole derivative modified with XMU-MP-9, which enhances the interaction between Nedd4-1 and K-Ras, promoting the ubiquitination and degradation of multiple K-Ras mutants, demonstrating anticancer potential. Fluconazole is an antifungal agent.

USP7-IN-4(USP7 inhibitor ALM4) is a non-competitive, potent and selective inhibitor of USP7 (ubiquitin-specific protease 7) with an IC50 = 6 nM, up-regulates p53 and p21, down-regulates MDM2, increases the level of ubiquitination of MDM2, and exhibits anti-proliferative activity in a variety of cancer cell lines, with an EC50 = 2.0 nM in RS4;11 (acute lymphoblastic leukemia cell line) .

LN-439A is a novel tetrahydro-β-carboline small molecule that acts as a potent catalytic inhibitor of the BAP1 deubiquitinase. It induces ubiquitination and degradation of the KLF5 transcription factor by binding to the catalytic pocket of BAP1. In basal-like breast cancer (BLBC) models, LN-439A significantly inhibits tumor cell proliferation and migration, induces G2/M phase arrest and apoptosis, and exhibits superior water solubility compared to existing BAP1 inhibitors. Furthermore, inhibition of BAP1 enzymatic activity by LN-439A also destabilizes its substrates, suggesting potential application value in inflammation-related diseases.

E3 ligase Ligand 8, a ligand for E3 ubiquitin ligase, can be connected to protein ligands through linkers to form PROTACs, which induce ubiquitination-mediated degradation of cancer-promoting proteins.

Triflupromazine is a dopamine receptor D1/D2 antagonist and LHDA inhibitor that suppresses dopamine activity in the central nervous system (CNS) and promotes LDHA-mediated AMBRA1 ubiquitination, used for treating mental disorders, sedation, and antiemesis.

Apcin-A is an anaphase-promoting complex (APC) inhibitor. It interacts strongly with Cdc20 and inhibits the ubiquitination of Cdc20 substrates. Apcin-A can be used to synthesize the PROTAC CP5V.