Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar (Mohali)-160 062, India.
Curr Drug Metab. 2021;22(9):683-697. doi: 10.2174/1389200222666210219122909.
Drug metabolism studies play a critical role in the optimization of the therapeutic efficacy of newer drug candidates. Many drug candidates and drugs were withdrawn from the pre-clinical/clinical stage or market due to the poor metabolic profiles. The poor metabolic profiles may make the clinical candidates/drugs inactive or toxic. Therefore, it is necessary to optimize the metabolic profiles at the initial phase of drug discovery and development processes. Recently, molecular modeling approaches were found to be useful in the optimization of metabolic profiles of clinical candidates. The molecular modeling approaches were employed in the identification of various metabolic profiles. In the present study, the current status of the research work on drug metabolism based on molecular modeling methodologies has been reviewed. The basics of drug metabolism and its importance in the physiological process of the human body have been described. Moreover, the involvement of molecular modeling approaches like pharmacophore- based modeling, QSAR, molecular docking, virtual screening, quantum chemical analysis, molecular dynamics, etc., in predicting metabolic profiles of therapeutic agents is analyzed. The present review provides computational insights in the prediction of substrate specificity, metabolic activity, SOM, metabolites, toxicity, etc., on cytochrome P450-mediated drug metabolism. The study may help the researchers to design novel drug candidates for the various classes of therapeutic targets with efficient metabolic profiles.
药物代谢研究在优化新型候选药物的治疗效果方面起着至关重要的作用。许多候选药物和药物由于代谢谱不佳而从临床前/临床阶段或市场撤回。代谢谱不佳可能使临床候选物/药物失去活性或有毒。因此，有必要在药物发现和开发过程的初始阶段优化代谢谱。最近，人们发现分子建模方法可用于优化临床候选物的代谢谱。这些分子建模方法被用于识别各种代谢谱。在本研究中，综述了基于分子建模方法的药物代谢研究工作的现状。描述了药物代谢的基础知识及其在人体生理过程中的重要性。此外，还分析了基于药效团的建模、QSAR、分子对接、虚拟筛选、量子化学分析、分子动力学等分子建模方法在预测治疗剂代谢谱中的作用。本综述为预测细胞色素 P450 介导的药物代谢中的底物特异性、代谢活性、SOM、代谢物、毒性等提供了计算见解。该研究可能有助于研究人员为具有高效代谢谱的各种治疗靶点设计新型候选药物。
