Ubiquitination

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.

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

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].

C004019 is a small molecule PROTAC capable of targeting tau for selective protein degradation from the cell, while recruiting tau and E3 ligase (Vhl) for selective enhancement of tau ubiquitination and proteollyzation. C004019 is a candidate for AD and related tau protein diseases.

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.

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.

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.

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。

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) .

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.

CYM5442 is an S1P agonist, targeting to Sphingosine.

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

1. Protosappanin B (Q-100961) significantly increases cell viability, inhibits cell apoptosis and up-regulates the expression of growth-associated protein 43. 2. Protosappanin B induces the degradation of p53 protein, via activation of a MDM2-dependent ubiquitination process.

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.

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.

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.

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

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.

CP5V, a PROTAC, induces mitotic inhibition, and suppresses cancer cell proliferation. It specifically degrades Cdc20 by linking Cdc20 to the VHL/VBC complex for ubiquitination followed by proteasomal degradation.

PROTAC Mcl1 degrader-1 is a Cereblon ligand-based targeted chimeric protein degrader (PROTAC), a selective Mcl-1 inhibitor. By hijacking the CRBN ubiquitin ligase to form a ternary complex with the target protein, it induces Mcl-1 ubiquitination. It can be used for cancer research.

MF-094 is a selective USP30 inhibitor with IC50 of 0.12 μM. MF-094 can increase protein ubiquitination and accelerate mitophagy.

CC0651 is an allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme that potently inhibits the ubiquitination of p27Kip1 (IC50: 1.72 μM).

Smurf1-IN-A01 (A01) is a ubiquitin ligase Smad ubiquitination regulatory factor-1 inhibitor (Kd: 3.664 nM) that enhances BMP-2 responsiveness by preventing Smurf1-mediated Smad1 5 degradation.

TZ9 is a selective and potent Rad6 inhibitor with anticancer and anti-tumor activity.TZ9 inhibits Rad6B-induced ubiquitination of histone H2A.TZ9 induces cell cycle arrest and apoptosis.