Abstract

IN SILICO DOCKING AND ADMET EVALUATION OF VORASIDENIB DERIVATIVES TARGETING IDH1

*Vaishnavi S. Pawar, Pranali J. Sabale, Sandhya P. Kadam, Dr. Prakash D. Jadhav

Abstract

Vorasidenib is a drug that blocks mutant isocitrate dehydrogenase enzymes. It is widely used in the treatment of IDH-mutant glioma. Changing its chemical structure can improve its performance. In this study, different derivatives of Vorasidenib were designed and tested using computational methods to identify compounds with stronger binding ability and better pharmacokinetic properties against IDH1. The pkCSM tool was used to study ADMET properties such as absorption, distribution, metabolism, excretion, and toxicity. Molecular docking was carried out using PyRx to examine how these derivatives interact with the target protein. The results showed that many derivatives formed strong interactions with the protein. Some compounds even showed similar or better binding affinity than the original drug. Cyclopropane -substituted analogue showed more stable interactions, which suggests that they may be useful as lead compounds for future drug development. The ADMET analysis showed that most of the compounds had good oral absorption, proper permeability, balanced distribution in the body, and acceptable toxicity levels. A few compounds showed concerns such as mutagenicity or weaker pharmacokinetic behavior. This study identified several promising Vorasidenib derivatives with improved therapeutic potential. The findings provide support for future laboratory studies and further research on optimized Vorasidenib analogues for glioma treatment.

Keywords: In silico study, Molecular docking, ADMET prediction, Drug design, Glioma, Derivative analysis.