Hct1 Inhibitors

Hct1 Inhibitors can be grouped based on their modes of direct and indirect action on Hct1's ubiquitin ligase functionality. Roscovitine, a CDK inhibitor, impairs the CDK1 activity that is integral to Hct1 function. Similarly, MLN4924 inhibits NAE, thereby limiting CRL and indirectly incapacitating Hct1. Apcin directly disrupts Hct1's capacity to bind to its substrates, effectively inhibiting the ubiquitination process. ProTAME impedes the assembly of the APC/C complex, affecting the role of Hct1 as an. UBEI-41 directly hinders the ubiquitin-proteasome system, reducing the ubiquitination capabilities of Hct1. ZM447439 specifically inhibits Aurora kinase, affecting the phosphorylation status of Hct1 and thereby altering its binding affinity for the APC/C complex.

Indirect inhibitors often modulate pathways that intersect with Hct1's role in the cell cycle or protein degradation. MG132, a proteasome inhibitor, negates Hct1 functionality by the degradation of its ubiquitinated targets. Cisplatin and Nutlin-3 affect the p53 pathway, which can, in turn, inhibit the CDK1-Cyclin B complex and thereby Hct1. Palbociclib and KU-55933 affect the cell cycle and DNA damage response, respectively, both leading to a modulation of CDK1 activity that ultimately affects Hct1. Wortmannin inhibits PI3K, affecting Akt signaling, and thereby influencing CDK1 activity, which is essential for Hct1 functionality.