J 2023

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

KUMAR, S Pranush, Tarang JADAV, Amit Kumar SAHU, Moumita Ghosh CHOWDHARY, Ankit SIWACH et. al.

Basic information

Original name

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

Authors

KUMAR, S Pranush, Tarang JADAV, Amit Kumar SAHU, Moumita Ghosh CHOWDHARY, Ankit SIWACH, Harit PATEL, Sagarkumar PATEL, Niraj RAJPUT, Amit SHARD, Amit Suresh KHAIRNAR (356 India, belonging to the institution) and Pinaki SENGUPTA (guarantor)

Edition

BIOMEDICAL CHROMATOGRAPHY, HOBOKEN, WILEY, 2023, 0269-3879

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 1.800 in 2022

RIV identification code

RIV/00216224:14110/23:00130692

Organization unit

Faculty of Medicine

UT WoS

000955749900001

Keywords in English

acute oral toxicity; IMID-2; LC-MS; MS; metabolic stability; pharmacokinetics

Tags

Tags

International impact, Reviewed
Změněno: 2/2/2024 11:45, Mgr. Tereza Miškechová

Abstract

V originále

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 the National Institute of Pharmaceutical Education and Research-Ahmedabad 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 a dose level of 175 mg/kg. Furthermore, a pharmacokinetic study of IMID-2 was also carried out using LC-MS/MS to understand its absorption, distribution, metabolism, and excretion profile. The molecule was found to have promising bioavailability through the oral route. This research work is thus another step in the drug testing of this promising anticancer molecule. The molecule can be considered to be a potential anticancer lead based on the earlier report substantiated by current findings.