Mechanistically, koumine disrupted the functional interaction between HSP90 and its co-chaperone CDC37, leading to the downregulation and inactivation of critical downstream client proteins, including cyclin-dependent kinases CDK4 and CDK6.<h4>Discussion</h4>These findings elucidate that koumine exerts potent anti-CRC effects primarily by targeting the HSP90-CDC37 chaperone complex and inhibiting the CDK4/6-Rb signaling axis. Here, CDK6 is linked to colorectal carcinoma.