E1/E2/E3 Enzyme Inhibitor

PRC1-IN-1 is a PRC1 complex inhibitor. PRC1-IN-1 binds to both RING1A and RING1B proteins, and inhibits the activities of RING1B-BMI1 and RING1B-PCGF1. PRC1-IN-1 effectively inhibits H2AK119 ubiquitination and induces cell differentiation in leukemia cells. PRC1-IN-1 can be used for the research of leukemia.

SENP1-IN-1 is a specific deSUMOylation protease 1 (SENP1) inhibitor extracted from patent CN110627860, Compound 29. SENP1-IN-1 is developed for tumor radiosensitivity enhancement.

TZ9 is a selective Rad6 inhibitor. TZ9 inhibits Rad6B-induced histone H2A ubiquitination, downregulates intracellular β-catenin, induces G2-M arrest and apoptosis, and inhibits the proliferation and migration of metastatic human breast cancer cells.

DCN1-UBC12-IN-4 (compound 5p) is an inhibitor of DCN1-UBC12, with an IC₅₀ greater than 10000 nM, and it exhibits anti-tumor activity.

UbcH5c-IN-1 (compound 6d) is a potent and selective small-molecule inhibitor of Ubiquitin-conjugating enzyme UbcH5c, with a K_d of 283 nM for E2 UbcH5c-IN-1 by covalent binding with Cys85. A promising lead compound for the development of new antirheumatoid arthritis (RA) agent.

WS-383 is a potent, selective and reversible inhibitor of DCN1-UBC12 interaction, with an IC₅₀ of 11 nM. WS-383 inhibits Cul3/1 neddylation, induces accumulation of p21, p27 and NRF2.

HECT E3-IN-1 (compound 3) is a HECT E3 ligase inhibitor. HECT E3-IN-1 (compound 3) disrupts Ub binding to the noncovalent Ub-binding site of Nedd4-1.

CTX1 is a p53 activator that overcomes HdmX-mediated p53 repression. CTX1 exhibits potent anti-cancer activity in a mouse acute myeloid leukemia (AML) model system.

Skp2-IN-4 is an Skp2 inhibitor with a IC₅₀ of 0.38  μM for Skp2-Cks1 binding. Skp2-IN-4 improves anti-tumor activity, inhibits the proliferation and induces S phase arrest by targeting Skp2. Skp2-IN-4 significantly enhances Cisplatin (HY-17394) chemosensitivity by suppressing the tumor cell stemness in NCl-H1299 xenograft mice model, promising for lung cancer and esophageal cancer research.

MuRF1-IN-2 (Example 3) is a MuRF1 inhibitor. MuRF1-IN-2 can be used for research of muscle wasting conditions, of skeletal or cardial muscle atrophy.

RO8994 (Compound 4) is an orally active, highly potent and selective spiroindolinone p53-MDM2 inhibitor with an IC₅₀ value of 5 nM (HTRF binding assays) and 20 nM (MTT proliferation assays). RO8994 induces up-regulation of p53 expression and Apoptosis in wild-type p53 cancer cells. RO8994 also inhibits tumor growth in the tumor xenograft model.

PROTAC MDM2 Degrader-2 is an MDM2 PROTAC degrader. PROTAC MDM2 Degrader-2 can induce the self-ubiquitination and degradation of MDM2, thereby upregulating the level of p53 protein. PROTAC MDM2 Degrader-2 has anti-tumor activity and can be used in the study of cancer.

MN714 is a prodrug of MN551 (HY-156395) with enhanced cell permeability. MN714 specifically and covalently binds to SOCS2 within living cells, with an EC₅₀ of 3.77 μM at 2 h and 2.52 μM at 8 h. MN714 serves as a chemical probe for investigating the biological mechanisms of the SOCS2 and CRL5 complex, and also functions as an E3 ligase linker for PROTAC development.

Hydrocotarnine is a Cbl inhibitor, and results in inflammasome-mediated IL-18 secretion in colitis. Hydrocotarnine increases expression of GLUT1 and cellular glucose uptake in glycolytic metabolism. Hydrocotarnine acts as an agent that provides analgesic effect in cancer research.

Cbl-b-IN-5 (compound 6) is a Cbl-b inhibitor (IC₅₀=3-10 µM). Cbl-b-IN-5 has the potential to be used in the study of cancer and related diseases amenable to immune system modulation.

NRX-2663 is an enhancer of the interaction between β-catenin, and its cognate E3 ligase, SCF^β-TrCP. NRX-2663 enhances the binding of β-catenin peptide for β-TrCP with an EC₅₀ of 22.9 μM and a K_d of 54.8 nM.

Cbl-b-IN-10 is a Cbl-b and c-Cbl inhibitor with IC₅₀ values of 6.0 nM and 3.5 nM, respectively. Cbl-b-IN-10 can be used in the study of cancer.

WSB1 Degrader 1 is an orally active WSB1 degrader that inhibits cancer cell migration. WSB1 Degrader 1 induces time- and concentration-dependent degradation of WSB1 in a proteasome-dependent manner, increases RhoGDI2 protein levels, and reduces WSB1-driven F-actin organization and membrane ruffling. WSB1 Degrader 1 can be used in studies of cancer metastasis.

XMU-MP-10 is a selective NEDD4 inhibitor with a K_D of 43.92 nM. XMU-MP-10 selectively inhibits NEDD4 auto-ubiquitination without affecting other ubiquitination activity, upregulates of β-TrCP and results YAP degradation without affecting NEDD4 protein expression. XMU-MP-10 exhibits significant in vivo efficacy in inhibiting TNBC tumor growth by enhancing CD8⁺ T cell infiltration. XMU-MP-10 enhances antitumor immune responses through the β-TrCP/YAP/ECM axis. XMU-MP-10 can be used for Triple-Negative Breast Cancer (TNBC) research.

p53 and MDM2 proteins-interaction-inhibitor dihydrochloride (Compound 32) is an inhibitor of the interaction between p53 and MDM2. p53 and MDM2 proteins-interaction-inhibitor dihydrochloride has potential applications in cancer research.