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CYP-mediated drug metabolism predictions using In silico methods:
Predicting drug metabolism by CYPs and understanding substrate specificity: During my Ph.D. tenure at NIPER, I designed and co-supervised several master’s thesis projects for their successful completion with publication in peer‑reviewed scientific journals. The issue of substrate specificity was explored and addressed for selected CYP isoforms using molecular docking, molecular dynamics simulations, (J. Mol. Recog. 2016, Protein J. 2014) and quantum mechanical (QM) studies (Mol. Divers. 2015). These studies showed the importance of QM descriptors, chemical hardness and local nucleophilicity, for prediction of drug metabolism and substrate specificity by CYP1 family enzymes.
CYP-mediated drug metabolism predictions using In vitro methods:
CytochromeP450 mediated drug metabolism prediction studies: These studies focused on the evolution of CYP inhibition potential by drug metabolites and their contribution to drug‑drug interactions (Biomed. Chromatogr. 2016), plasma protein binding, pharmacokinetics, tissue distribution of drugs and their metabolites (J. Pharm. Biomed. Anal. 2015, J. Mass Spectrom. 2014). I used molecular docking to predict drug metabolism by CYPs and TOPKAT and DEREK to predict the potential toxicities of drug metabolites. The insights gained from in silico analysis were then used by experimental collaborators to develop a protocol for drug metabolism studies. As my Master’s thesis project, I worked on an industry-academia collaborative project with Eli Lilly. We developed and optimized a homology modeling and molecular docking based protocol for efficient prediction of CYP mediated drug metabolism of new chemical entities.
Publications:
Publications:
- Siddharth S Kesharwani, Prajwal P Nandekar*, Preeti Pragyan, Vijay Rathod, Abhay T Sangamwar; Characterization of differences in substrate specificity among CYP1A1, CYP1A2 and CYP1B1: an integrated approach employing molecular docking and molecular dynamics simulations, 2016, Journal of Molecular Recognition, Volume 29 (8), Pages 370-390, IF: 2.175.
- Preeti Pragyan, Siddharth S Kesharwani, Prajwal P Nandekar*, Vijay Rathod, Abhay T Sangamwar; Predicting drug metabolism by CYP1A1, CYP1A2, and CYP1B1: insights from MetaSite, molecular docking and quantum chemical calculations, 2014, Molecular Diversity, Volume 18 (4), Pages 865-878, IF: 1.752.
- Siddharth S Kesharwani, Prajwal P Nandekar*, Preeti Pragyan, Abhay T Sangamwar; Comparative proteomics among cytochrome P450 family 1 for differential substrate specificity, 2014, Protein journal, Volume 33 (6), Pages 536-548, IF: 1.139.
- Roshan M Borkar, Murali Mohan Bhandi, Ajay P Dubey, V Ganga Reddy, Prashanth Komirishetty, Prajwal P Nandekar, Abhay T Sangamwar, Ahmed Kamal, Sanjay K Banerjee, R Srinivas; An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug–drug and drug–herb interaction by LC‐ESI/MS/MS, 2016, Biomedical Chromatography, Volume 30 (10), Pages 1556-1572, IF: 1.613.
- Roshan M Borkar, Murali Mohan Bhandi, Ajay P Dubey, Prajwal P Nandekar, Abhay T Sangamwar, Sanjay K Banerjee, R Srinivas; Plasma protein binding, pharmacokinetics, tissue distribution and CYP450 biotransformation studies of fidarestat by ultra high performance liquid chromatography–high resolution mass spectrometry, 2015, Journal of Pharmaceutical and Biomedical Analysis, Volume 102, Pages 386-399, IF: 3.255.
- Pradipbhai D Kalariya, B Raju, Roshan M Borkar, Deepak Namdev, S Gananadhamu, Prajwal P Nandekar, Abhay T Sangamwar, R Srinivas; Characterization of forced degradation products of ketorolac tromethamine using LC/ESI/Q/TOF/MS/MS and in silico toxicity prediction, 2014, Journal of Mass Spectrometry, Volume 49 (5), Pages 380-391, IF: 2.422.
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