CKS1 inhibitor

A CKS1 inhibitor is a therapeutic agent designed to target and inhibit cyclin-dependent kinase regulatory subunit 1 (CKS1), a critical accessory protein of the SCF-Skp2 (Skp1-Cullin1-F-box) ubiquitin ligase complex. CKS1 is essential for the ubiquitin-mediated proteasomal degradation of key cell cycle regulators, most notably the cyclin-dependent kinase inhibitor p27 (p27Kip1). By blocking the interaction between Skp2 and CKS1, or directly inhibiting CKS1, these agents stabilize p27 levels, leading to cell cycle arrest and apoptosis in rapidly proliferating cancer cells. In preclinical models of acute myeloid leukemia (AML), CKS1 inhibition has demonstrated a dual therapeutic benefit: it selectively depletes leukemic stem cells (LSCs) by inducing lethal reactive oxygen species (ROS) accumulation via RAC1 hyperactivation, while simultaneously protecting healthy hematopoietic stem and progenitor cells (HSPCs) from chemotherapeutic toxicity by inducing a state of protective quiescence.

Other names

CKS1iCKS-1iCKS 1iCks1 inhibitorCks-1 inhibitorCks 1 inhibitorSCF-SKP2-CKS1 inhibitorSCF-SKP-2-CKS1 inhibitorSCF-SKP 2-CKS1 inhibitorSKP2-CKS1 inhibitorSKP-2-CKS1 inhibitorSKP 2-CKS1 inhibitorcyclin-dependent kinase regulatory subunit 1 inhibitor