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.
bioRxiv : the preprint server for biology. 2023 Jul 03*** epublish ***
Takuma Uo, Kayode K Ojo, Cynthia C Sprenger, Kathryn Soriano Epilepsia, B Gayani K Perera, Mamatha Damodarasamy, Shihua Sun, Soojin Kim, Hannah H Hogan, Matthew A Hulverson, Ryan Choi, Grant R Whitman, Lynn K Barrett, Samantha A Michaels, Linda H Xu, Haley J Pang, Matthew M Nguyen, Anna-Lena B G Vigil, Varun Kamat, Lucas B Sullivan, Ian R Sweet, Ram Vidadala, Dustin J Maly, Wesley C Van Voorhis, Stephen R Plymate