A Compound that Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer.
Takuma UoKayode K OjoCynthia C T SprengerKathryn Soriano EpilepsiaB Gayani K PereraMamatha DamodarasamyShihua SunSoojin KimHannah R Hapner HoganMatthew A HulversonRyan ChoiGrant R WhitmanLynn K BarrettSamantha A MichaelsLinda H XuHaley J PangMatthew M NguyenAnna-Lena B G VigilVarun KamatLucas B SullivanIan R SweetRam VidadalaDustin J MalyWesley C Van VoorhisStephen R PlymatePublished in: bioRxiv : the preprint server for biology (2023)
Metastatic castration-resistant prostate cancer remains incurable regardless of recent therapeutic advances. Tumors display highly glycolytic phenotypes as the cancer progresses. In this study, we report the preclinical activity and characterization of a novel series of small molecules with antiglycolytic activity mediated through inhibition of hexokinase 2. These compounds display selective growth inhibition across multiple prostate cancer models. We describe a lead compound (BKIDC-1553) that demonstrates promising pharmacological properties and activity in preclinical models of advanced prostate cancer. This work supports testing BKIDC-1553 and its derivatives in clinical trials for patients with advanced prostate cancer.