Apcin

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[1][2][3].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> APC

Apcin (25-50 μM; 48 hours) significantly increases MM apoptosis combining with proTAME (6, 12 μM)[3]. Apcin (25 μM; 2-14 hours) induces slippage more slowly[2]. Apcin (50-200 μM) stabilizes cycB1-NT and securin most effectively, with somewhat weaker effects against full-length cyclin B1[1]. Apcin (1.5-200 μM; 18 hours) synergizes with proTAME (a cell-permeable TAME prodrug) to prolong mitotic duration in RPE1 cells[1]. Apoptosis Analysis[3] Cell Line: HMCLs LP-1 and RPMI-8226 cells Concentration: 25, 50 μM Incubation Time: 48 hours Result: Had minor effects on multiple myeloma (MM) cells alone and significantly increased MM apoptosis combining with proTAME (6, 12 μM). Western Blot Analysis[2] Cell Line: HeLa cells with Nocodazole (100 nM) Concentration: 25 μM Incubation Time: 2-14 hours Result: Induced slippage more slowly, as indicated by Cdc27 dephosphorylation and a reduction in cyclin B1, securin and phosphoH3 levels beginning 4-6h after mitotic entry.

[1]. Katharine L Sackton, et al. Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C. Nature. 2014 Oct 30;514(7524):646-9.

[2]. Katherine V Richeson, et al. Paradoxical mitotic exit induced by a small molecule inhibitor of APC/C Cdc20. Nat Chem Biol. 2020 May;16(5):546-555.

[3]. Susanne Lub, et al. Inhibiting the anaphase promoting complex/cyclosome induces a metaphase arrest and cell death in multiple myeloma cells. Oncotarget. 2016 Jan 26;7(4):4062-76.