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

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:

URL

Impact factor

Impact factor: 1.800 in 2022

RIV identification code

RIV/00216224:14110/23:00130692

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/bmc.5618

UT WoS

000955749900001

Keywords in English

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

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.

Citovat

KUMAR, S Pranush, Tarang JADAV, Amit Kumar SAHU, Moumita Ghosh CHOWDHARY, Ankit SIWACH, Harit PATEL, Sagarkumar PATEL, Niraj RAJPUT, Amit SHARD, Amit Suresh KHAIRNAR and Pinaki SENGUPTA. 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. BIOMEDICAL CHROMATOGRAPHY. HOBOKEN: WILEY, 2023, vol. 37, No 6, p. 1-8. ISSN 0269-3879. Available from: https://dx.doi.org/10.1002/bmc.5618.

@article{2279443,
   author = {Kumar, S Pranush and Jadav, Tarang and Sahu, Amit Kumar and Chowdhary, Moumita Ghosh and Siwach, Ankit and Patel, Harit and Patel, Sagarkumar and Rajput, Niraj and Shard, Amit and Khairnar, Amit Suresh and Sengupta, Pinaki},
   article_location = {HOBOKEN},
   article_number = {6},
   doi = {http://dx.doi.org/10.1002/bmc.5618},
   keywords = {acute oral toxicity; IMID-2; LC-MS; MS; metabolic stability; pharmacokinetics},
   language = {eng},
   issn = {0269-3879},
   journal = {BIOMEDICAL CHROMATOGRAPHY},
   title = {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},
   url = {https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/bmc.5618},
   volume = {37},
   year = {2023}
}

TY  - JOUR
ID  - 2279443
AU  - Kumar, S Pranush - Jadav, Tarang - Sahu, Amit Kumar - Chowdhary, Moumita Ghosh - Siwach, Ankit - Patel, Harit - Patel, Sagarkumar - Rajput, Niraj - Shard, Amit - Khairnar, Amit Suresh - Sengupta, Pinaki
PY  - 2023
TI  - 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
JF  - BIOMEDICAL CHROMATOGRAPHY
VL  - 37
IS  - 6
SP  - 1-8
EP  - 1-8
PB  - WILEY
SN  - 02693879
KW  - acute oral toxicity
KW  - IMID-2
KW  - LC-MS
KW  - MS
KW  - metabolic stability
KW  - pharmacokinetics
UR  - https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/bmc.5618
N2  - 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.
ER  -

KUMAR, S Pranush, Tarang JADAV, Amit Kumar SAHU, Moumita Ghosh CHOWDHARY, Ankit SIWACH, Harit PATEL, Sagarkumar PATEL, Niraj RAJPUT, Amit SHARD, Amit Suresh KHAIRNAR and Pinaki SENGUPTA. 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. \textit{BIOMEDICAL CHROMATOGRAPHY}. HOBOKEN: WILEY, 2023, vol.~37, No~6, p.~1-8. ISSN~0269-3879. Available from: https://dx.doi.org/10.1002/bmc.5618.

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