Computational Identification of Stearic Acid as a Potential PDK1 Inhibitor and In Vitro Validation of Stearic Acid as Colon Cancer Therapeutic in Combination with 5-Fluorouracil

• Authors: Jonathan Mitchel, Emory University; Pratima Bajaj, Georgia Institute of Technology; Ketki Patil, Emory University; Austin Gunnarson, Emory University; Emilie Pourchet, Emory University; Yoo Na Kim, Emory University; Jeffrey Skolnick, Georgia Institute of Technology; Balakrishna S Pai, Emory University
• Journal Title: Cancer Informatics
• Volume: Volume 20
• Publisher: Libertas Academica | 2021-12-13
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1177/11769351211065979
• Keywords: Computational tool - FINDSITEcomb; stearic acid; 5-FU; flow cytometry

Abstract

Colorectal cancer is the third largest cause of cancer-related mortality worldwide. Although current treatments with chemotherapeutics have allowed for management of colorectal cancer, additional novel treatments are essential. Intervening with the metabolic reprogramming observed in cancers called “Warburg Effect,” is one of the novel strategies considered to combat cancers. In the metabolic reprogramming pathway, pyruvate dehydrogenase kinase (PDK1) plays a pivotal role. Identification and characterization of a PDK1 inhibitor is of paramount importance. Further, for efficacious treatment of colorectal cancers, combinatorial regimens are essential. To this end, we opted to identify a PDK1 inhibitor using computational structure-based drug design FINDSITEcomb and perform combinatorial studies with 5-FU for efficacious treatment of colorectal cancers.