APC Inhibitor

proTAME, a cell-permeable proagent form of TAME, is an anaphase promoting complex/cyclosome (APC/C) inhibitor. proTAME causes cell cycle arrest in metaphase.

Apcin, a ligand of Cdc20, is a potent and competitive anaphase-promoting complex/cyclosome (APC/C(Cdc20)) E3 ligase activity inhibitor. Apcin competitively inhibits APC/C-dependent ubiquitylation by binding to Cdc20 and preventing substrate recognition. Apcin occupes the D-box-binding pocket on the side face of the WD40-domain and can prolong mitosis.

TAME is an inhibitor of anaphase-promoting complex/cyclosome (APC/C or APC), which binds to APC/C and prevents its activation by Cdc20 and Cdh1, produces mitotic arrest. TAME is not cell permeable.

Ferroptosis inducer-16 (anti-NSCLC agent-2) is a nitric oxide (NO) donor and a ferroptosis inducer. Ferroptosis inducer-16 inhibits DNA synthesis and colony formation. Ferroptosis inducer-16 disrupts lysosomal integrity by releasing NO, triggers iron overload and oxidative stress, downregulates the SLC7A11-GPX4 axis, depletes GSH, and accumulates lipid peroxides. Ferroptosis inducer-16 inhibits tumor growth in an OVCAR8/ADR xenograft mouse model without obvious toxicity, and can be used in the study of non-small cell lung cancer and drug-resistant ovarian cancer.

Apcin-A is a small molecule inhibitor that selectively targets the cell division cycle protein Cdc20 and is a derivative of Apcin (HY-110287). Apcin-A competitively binds to the D-box binding pocket of Cdc20 and inhibits substrate ubiquitination mediated by the anaphase promoting complex APC/C-Cdc20. Apcin-A also blocks the binding of Cdc20 to substrates (such as securin and cyclin B1), inhibiting anaphase initiation and cell cycle exit. Apcin-A can promote or prolong mitotic slippage in coordination with p31^comet under conditions of high spindle assembly checkpoint (SAC) activity. Apcin-A can be used to develop anti-mitotic drugs and overcome tumor chemotherapy resistance. Apcin-A can be used to synthesize PROTAC CP5V (HY-130257)[1][2][3].

TAME hydrochloride is an inhibitor of anaphase-promoting complex/cyclosome (APC/C or APC), which binds to APC/C and prevents its activation by Cdc20 and Cdh1, produces mitotic arrest. TAME hydrochloride is not cell permeable.

CDC20/HSP90-IN-1 (Compound 2b) is a Cdc20/Hsp90 inhibitor with a K_d of 16.2 μM for Cdc20 and a K_d of 0.241 μM for Hsp90α. CDC20/HSP90-IN-1 exerts potent antitumor activity through reducing p53-mediated Cdc20, upregulating Bim, downregulating Cyclin B1 expression, and disturbing B-Raf and AKT pathways via destroying Hsp90 chaperone function. CDC20/HSP90-IN-1 overcomes Vemurafenib (HY-12057)-induced resistant melanoma.

CDC20-IN-2 (14c), a Cdc20 inhibitor (K_D: 7.65 μM), causes G2/M phase arrest and promotes DNA damage accumulation. CDC20-IN-2 (14c) stabilizes key substrates such as Cyclin B1 and Bim, leading to enhanced apoptosis and suppression of tumor cell proliferation and migration.

MAI-400 is an APC-Asef interaction inhibitor (K_d = 12 nM, IC₅₀ = 250 nM). MAI-400 can be used in the research of colorectal cancer.

Apcin-A monohydrochloride, an Apcin derivative, is an anaphase-promoting complex (APC) inhibitor. Apcin-A monohydrochloride interacts strongly with Cdc20, and inhibits the ubiquitination of Cdc20 substrates. Apcin-A monohydrochloride can be used to synthesize the PROTAC CP5V (HY-130257).