Assessment of metabolic stability, pharmacokinetics by LC-MS/MS and establishment of safe dose of IMID-2, a novel anticancer molecule under drug discovery.

Abstract

Pyruvate kinase (PK) M2 activators ramp up glycolysis in cancer cells leading to a reversal of the Warburg effect in cancer cells. A promising PKM2 activator molecule IMID-2 developed by National Institute of Pharmaceutical Education & Research, Ahmedabad (NIPER-A) showed promising anticancer activity against MCF-7 and COLO-205 cell lines which represent breast and colon cancer. Its physicochemical properties like solubility, ionization constant, partition coefficient, and distribution constant have already been established. Its metabolic pathway is also well established through in vitro and in vivo metabolite profiling and reported previously. In this study, we have evaluated the metabolic stability of IMID-2 using (LC-MS/MS and investigated the safety aspect of the molecule through an acute oral toxicity study. In vivo studies in rats confirmed that the molecule is safe even at the dose level of 175 mg/kg. Furthermore, the pharmacokinetic study of IMID-2 was also carried out by LC-MS/MS to understand its ADME profile. The molecule was found to have promising bioavailability through the oral route. This research work is thus another step toward drug-likeness testing of this promising anti-cancer molecule. The molecule can be considered to be a potential anti-cancer lead based on the earlier report substantiated by current findings.