APC13 Inhibitors

APC13 inhibitors are a class of chemicals that specifically target the activity of the anaphase-promoting complex subunit 13 (APC13). The APC13 protein is a component of the anaphase-promoting complex/cyclosome (APC/C), which is a cell cycle-regulated E3 ubiquitin ligase responsible for controlling progression through mitosis and the G1 phase of the cell cycle. These inhibitors can directly inhibit the function of APC13 by targeting its interaction with other components of the APC/C complex or by interfering with its enzymatic activity. For example, MG-132 [Z-Leu- Leu-Leu-CHO] binds to the catalytic site of the proteasome, preventing the degradation of target proteins by blocking the proteolytic activity of the enzyme. MLN4924 inhibits the neddylation of cullin-RING ligases (CRLs), including the APC/C complex, leading to the stabilization of APC/C substrates andthe inhibition of cell cycle progression. Reversine, caffeine, curcumin, and thalidomide all disrupt the normal function of the APC/C complex by inhibiting key regulators such as Aurora kinases and cyclin-dependent kinases (CDKs). These inhibitors interfere with the phosphorylation and activation of APC/C, leading to the inhibition of cell cycle progression.

TAME and ProTAME directly target the APC/C complex itself, binding to its components and preventing its activation. ZM-447439, RO-3306, MLN8237, and NSC 625987 inhibit the activity of Aurora kinases, which are involved in regulating mitotic progression and spindle assembly. By inhibiting Aurora kinases, these compounds disrupt the normal function of the APC/C complex and inhibit cell cycle progression. In summary, APC13 inhibitors are a diverse class of chemicals that directly target the activity of the APC/C complex or indirectly inhibit its function by interfering with key regulators of the cell cycle. These inhibitors can disrupt the interaction between APC/C and its coactivators, inhibit the enzymatic activity of the complex, or interfere with the phosphorylation and activation of APC/C. By inhibiting APC/C, these compounds can effectively inhibit cell cycle progression and potentially have implications in the regulation of cell growth and division.