ubiquitination in 1

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

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.

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

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].

CaMKIIα-PHOTAC is a photochemically targeted chimera (PHOTAC) that specifically targets Ca2+ calmodulin-dependent protein kinase II α (CaMKIIα), facilitating its ubiquitination and subsequent proteasome-mediated degradation when exposed to specific light wavelengths. Under illumination, CaMKIIα-PHOTAC diminishes synaptic functions and weakens evoked field excitatory postsynaptic potentials in the mouse hippocampus, impacting physiological responses and sustaining long-term potentiation and memory functions within dendritic domains [1].

PROTAC IDO1 Degrader-1, a pioneering compound, efficiently targets indoleamine 2,3-dioxygenase 1 (IDO1) for ubiquitination and degradation by recruiting IDO1 to the CRBN E3 ligase, thereby facilitating its entry into the ubiquitin-proteasome system (UPS) with a DC50 of 2.84 μM. This compound also moderately enhances the tumor-killing efficacy of HER2 CAR-T cells[1].

SCH529074 is a selective activator of p53 (Ki = 1 μM) and can be used in studies about non-small-cell lung carcinoma. SCH529074 restores mutant p53 function and interrupts HDM2-mediated ubiquitination of wild Type p53.

TEAD-IN-2 is an innovative, orally bioavailable inhibitor that targets the transcriptional enhancer associate domain (TEAD). It functions by regulating TEAD through ubiquitination and/or degradation by specific compounds. This compound, TEAD-IN-2, holds potential for studying various diseases, disorders, or conditions linked to TEAD [1].

E3 ligase Ligand 10 serves as a ligand for E3 ubiquitin ligase and can be conjugated to a protein ligand through a linker, resulting in the formation of PROTACs. These PROTACs act as inducers of ubiquitination-mediated degradation, specifically targeting cancer-promoting proteins[1].

EN219 is a synthetic recruiter of the E3 ubiquitin ligase RNF114.1It binds to cysteine 8 (C8) in the intrinsically disordered region of RNF114 (RNF114-C8; IC50= 470 nM) and inhibits RNF114-induced autoubiquitination and p21 ubiquitination in a cell-free assay when used at a concentration of 50 μM. EN219 (1 μM) also interacts with cysteine residues in the tubulin β1 chain (TUBB1), heat shock protein 60 (Hsp60), also known as Hsp family D member 1 (HspD1), and histone H3.1 (HIST1H3A) in 231MFP human breast cancer cells in a proteomic profiling assay. It has been linked to the bromodomain and extra terminal domain (BET) inhibitor ligand (+)-JQ1 for use as a proteolysis-targeting chimera (PROTAC) to degrade bromodomain-containing protein 4 (BRD4) in 231MFP cells. 1.Luo, M., Spradlin, J.N., Boike, L., et al.Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product functionCell Chem. Biol.28(4)559-566(2021)

γ-AA peptide P6 acts as a potent activator of E6 associated protein (E6AP), facilitating both its self-ubiquitination and the ubiquitination of E6AP substrates in vitro reconstituted reactions. Furthermore, γ-AA peptide P6 amplifies substrate ubiquitination within the cell, thereby expediting their proteasomal degradation [1].

A11, a cell-penetrating peptide, integrates the HIV-1 Tat protein transduction domain with an 11-amino acid segment from the annexin A1 N-terminus (residues 20-30). This compound disrupts the interaction between annexin A1 and the Eph receptor tyrosine kinase A2 (EphA2), leading to enhanced EphA2 ubiquitination in HK1 nasopharyngeal carcinoma (NPC) cells. At a concentration of 10 µM, A11 curtails proliferation, migration, and invasion of HK1 and 5-8F NPC cells. Furthermore, A11 demonstrably diminishes tumor volume in mouse xenograft models of 5-8F and HK1 NPC in vivo.

β-Naphthoflavone-CH2-OH (β-NF-CH2-OH) serves as an AhR E3 ligase ligand, forming chimeric molecules when connected to a protein ligand through a linker, resulting in PROTACs or SNIPERs (e.g., β-naphthoflavone-JQ1). These chimeric molecules recruit the AhR E3 ligase complex by incorporating AhR ligands. By inducing ubiquitination-mediated degradation, PROTACs effectively target and degrade cancer-promoting proteins [1].

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].

DA-PROTAC is a potent degrader of the copper ion-transport proteins Atox1 and CCS, capable of binding to both proteins and facilitating their association with E3 ligase. This interaction enhances the ubiquitination and subsequent proteasomal degradation of Atox1 and CCS. DA-PROTAC is utilized in triple negative breast cancer research [1].

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.

Nrf2 activator-2 (referred to as compound O15), an Osthole derivative, is a highly potent Nrf2 agonist exhibiting an EC 50 of 2.9 μM in 293 T cells. By effectively disrupting the binding between Keap1 and Nrf2, Nrf2 activator-2 activates the Nrf2 pathway. Furthermore, this compound significantly reduces the ubiquitination of Nrf2 in cells, indicating its potential in regulating Nrf2 activity [1].

HB007 is a potent degrader of small ubiquitin-related modifier 1 (SUMO1). It mediates the ubiquitination and subsequent degradation of SUMO1, leading to a decrease in tumor growth in vivo. HB007 is a valuable tool for investigating brain, breast, colon, and lung cancers[1][2].