Research Paper|Volume 14, Issue 13|pp 5478—5492

Computational study on novel natural compound inhibitor targeting IDH1_R132H

Baolin Zhou², Fang Yang², Lei Qin², Jun Kuai², Lu Yang², Lanfang Zhang², Peisheng Sun³, Guangpeng Li⁴, Xinhui Wang¹

¹Department of Oncology, First People's Hospital of Xinxiang, Xin Xiang 453100, China
²Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical College, Xin Xiang 453100, China
³Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinxiang Medical College, Xin Xiang 453100, China
⁴Department of Emergency, The First Affiliated Hospital of Xinxiang Medical College, Xin Xiang 453100, China

Received: September 17, 2021Accepted: June 27, 2022Published: July 7, 2022

https://doi.org/10.18632/aging.204162

Copyright: © 2022 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Isocitrate dehydrogenases (IDH) catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. IDH1 mutation has been reported in various tumors especially Cholangiocarcinoma, while the IDH1_R132H is reported to be the most common mutation of IDH1. IDH1_R132H inhibitors are effective anti-cancer drugs and have shown significant therapeutic effects in clinical. In this study, two novel natural compounds were identified to combine respectively with IDH1_R132H with a stronger binding force with conductive to interaction energy. They also showed low toxicity potential. Molecular dynamics simulation analysis demonstrated that the candidate ligands-IDH1_R132H complexes is stable in natural circumstances with favorable potential energy. Thus, Styraxlignolide F and Tremulacin were screened as promising IDH1_R132H inhibitors. We provide a solid foundation for the design and development of IDH1_R132H targeted drugs.