Dr. Rajnish
Faculty Profile
I am working as an Associate Professor in the Department of Pharmaceutical Engineering & Technology at the Indian Institute of Technology (BHU), Varanasi since November 2024. I obtained my Ph.D. degree in Pharmaceutical Sciences from the University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India in 2014 on the topic "Synthesis and study on azasteroids as 5α-reductase inhibitors." Soon after the Ph.D. thesis defense in April 2014, I moved to the Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden as a postdoctoral research associate, working with Prof. Taher Darreh-Shori and Prof. Bengt Winblad.
In June 2019, I accepted an Assistant Professor position at the Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden, and moved to India in November 2019.
I have also been awarded the Japan Society for the Promotion of Science summer fellowship to work in the Mizuguchi lab headed by Prof. Kenji Mizuguchi at NIBIOHN, Osaka, Japan during the summer of 2019. My main interests during my stay in Japan were to use Bioinformatics tools such as TargetMine developed by the Mizuguchi lab to discover novel drug targets using multi-omics data and AI/ML-based tools for pharmacokinetic properties prediction. My current research work is focused on the design, synthesis, and evaluation of potential therapeutics for the treatment of neurodegenerative diseases and to tackle antimicrobial resistance.
Teaching
PG Courses
- PH522: Advances in Drug Synthesis
- PH523: Chemistry of Natural Products
- PH536: Toxicology
UG Courses
- PH421: Computational Chemistry
- PH251: Pharmaceutical Analysis
- PH331: General Pharmacotherapeutics
- PH333: Drug Discovery Technology
- PH222: Bio-organic and Medicinal Chemistry
- PH321: Chemistry of Synthetic Drugs
- PH323: Principles and Techniques in Molecular Biology
Memberships of Professional Societies
- Life member of the Indian Society of Chemists and Biologists (ISCB)
- Life member of the Association of Pharmaceutical Teachers of India (APTI)
- Life member of the Indian Pharmacy Graduates Association (IPGA)
- Regular member of the Swedish Neuroscience Society (SNS)
- Life member of the Society for Neurochemistry, India (SNCI)
- Life member of the Bioinformatics and Drug Discovery Society (BIDDS)
Our Research Projects
1. Design and Synthesis of Natural Product-Inspired Molecules to Target Protein Aggregation in Neurodegenerative Diseases
Protein aggregation plays a pivotal role in the progression of many neurodegenerative diseases, making it a critical drug target for therapeutic intervention. Our research focuses on the design and synthesis of small molecules inspired by natural products to target these aggregation processes in disorders like Alzheimer's and Parkinson's disease. We are specifically developing compounds that can modulate the aggregation of proteins such as amyloid-beta and tau in Alzheimer's disease, as well as alpha-synuclein in Parkinson's disease. By targeting these aggregation pathways, we aim to prevent or mitigate the toxic effects of protein accumulation that drive neurodegeneration.
Key publications:
- Synthesis and biological evaluation of Halogen-Substituted novel α-Ketoamides as potential protein aggregation modulators in Alzheimer’s disease.
- Structure-based discovery of small molecule inhibitors of FKBP51-Hsp90 protein-protein interaction.
- Synthesis, single crystal X-ray, DFT, spectroscopic, molecular docking studies and in vitro biological evaluation of compound N-benzyl-4-(4-chlorophenyl)-2-oxobutanamide.
2. Discovery and Development of Choline Acetyltransferase (ChAT) ligands for Early Diagnosis of Alzheimer's Disease
Alzheimer's disease and related dementias present significant challenges, making early diagnosis crucial for improving therapeutic outcomes. Growing scientific evidence identifies the cholinergic enzyme ChAT (choline acetyltransferase), essential for acetylcholine biosynthesis, as a promising in vivo target for developing ligands that could serve as probes for early diagnosis or therapeutic monitoring. Despite its potential, no imaging ligands for ChAT are currently available. Our research is focused on filling this gap by designing and developing novel ligands that can be utilized as probes for imaging, including PET tracers, to target ChAT. This multidisciplinary effort involves the computational design, synthesis of potential candidates, in vitro and in vivo studies. We aim to develop valuable tools for early detection and monitoring therapeutic responses in Alzheimer's and related dementias.
Key publications:
- Discovery of novel choline acetyltransferase inhibitors using structure-based virtual screening.
- Mechanistic Insight into the Inhibition of Choline Acetyltransferase by Proton Pump Inhibitors
- Proton pump inhibitors act with unprecedented potencies as inhibitors of the acetylcholine biosynthesizing enzyme—A plausible missing link for their association with incidence of dementia
- Allosteric Binding Sites of Aβ Peptides on the Acetylcholine Synthesizing Enzyme ChAT as Deduced by In Silico Molecular Modeling
3. AI/ML-enabled Discovery and Development of Lead Compounds
AI and ML have revolutionized the discovery and development of lead compounds by significantly accelerating and refining the process. We utilized AI/ML for virtual screening of large chemical libraries, Deep Learning for predictive modeling of ADMET parameters, and Generative modeling for de novo drug design for a variety of diseases such as diabetes, antimicrobial resistance, cancer, and neurodegeneration. This approach enhances precision in drug design, facilitating the rapid development of effective lead molecules.
Key publications:
- Integrated use of ligand and structure-based virtual screening, molecular dynamics, free energy calculation and ADME prediction for the identification of potential PTP1B inhibitors.
- N-glycosylation induced changes in tau protein dynamics reveal its role in tau misfolding and aggregation: A microsecond long molecular dynamics study.
- Targeting SARS-CoV-2 main protease: structure based virtual screening, in silico ADMET studies and molecular dynamics simulation for identification of potential inhibitors.
- Artificial intelligence assisted identification of potential tau aggregation inhibitors: ligand- and structure-based virtual screening, in silico ADME, and molecular dynamics study.
Research Grants
| S.NO. | Project Title | Funding Agency | PI/Co-PI | Amount | Duration |
|---|---|---|---|---|---|
| 1. | Lead optimization and in vivo proof-of-concept studies of novel alpha-ketoamide based protein aggregation modulators for Alzheimer’s Disease | ICMR, New Delhi, India | Principal Investigator | 45,37,306 INR |
Jan 2025- Dec 2027 (Ongoing) |
| 2. | Discovery of novel selective inhibitors of choline acetyltransferase: lead optimization and in vivo pharmacokinetic studies | SERB-SRG, India | Principal Investigator | 32,86,840 INR | Jan, 2022–Dec, 2023 (Completed) |
| 3. | Development of a toolkit for prediction of blood-brain-barrier permeability using deep learning to expedite CNS drug discovery | SERB-MATRICS, India | Principal Investigator | 6,60,000 INR | Jan, 2022–Dec, 2024 (Completed) |
| 4. | Development of Novel Therapeutics for the Redemption from Burn and Frostbite Burn Injury Induced Pain in Military Veterans | SERB, India | Co-Investigator PI: Dr. Vinod Tiwari, IIT(BHU), India |
40,81,240 INR | Jan, 2021 – Dec, 2023 (Completed) |
| 5. | Machine learning-based design, synthesis, and evaluation of novel tau-aggregation inhibitors for the treatment of tauopathy in neurodegenerative diseases | Seed Grant IIT(BHU), India |
Principal Investigator | 10,00,000 INR | Jan, 2020 – Jan, 2021 (Completed) |
| 6. | Development of novel modulators of molecular chaperone network with focus on Alzheimer disease therapy | The Swedish Research Council, Sweden | Co-Investigator PI: Prof. Bengt Winblad, Karolinska Institutet, Sweden |
7.2 M SEK ~ 6.16 Crores INR | Jan, 2019 – Dec, 2022 (Completed) |
| 7. | Targeting the core cholinergic cells for development of biomarkers and therapeutic strategies in Alzheimer´s disease | The Swedish Research Council, Sweden | Co-Investigator PI: Prof. Taher Darreh-Shori, Karolinska Institutet, Sweden |
2.8 M SEK ~ 2.4 Crores INR | Jan, 2017 – Dec, 2020 (Completed) |
| 8. | Novel Lead Chat-PET Tracer As Early Diagnostic And Theragonistic Biomarker | Alzheimer's Association, United States | Co-Investigator PI: Prof. Taher Darreh-Shori, Karolinska Institutet, Sweden |
100,000 USD ~ 73.5 Lakhs INR | Jan, 2016 – Jan, 2018 (Completed) |
| 9. | Sigurd and Elsa Goljes Memory Foundation | Principal Investigator | 40000 SEK ~ 3.5 Lakhs INR | Jan, 2017 – Dec, 2018 (Completed) | |
| 10. | Gun and Bertil Stohnes foundation | Principal Investigator | 120000 SEK ~ 10.25 Lakhs INR | 2014–2018 | |
| 11. | Lars Hiertas Memory foundation | Principal Investigator | 100000 SEK ~ 8.5 Lakhs INR | 2016–2017 | |
| 12. | Tore Nilsons foundation for medical research | Principal Investigator | 130000 SEK ~ 11.15 Lakhs INR | 2015–2016 | |
| 13. | Foundation for old servants | Principal Investigator | 280000 SEK ~ 8.5 Lakhs INR | 2015, 2017–2018 | |
| 14. | Gunvor and Josef Aners foundation | Principal Investigator | 150000 SEK ~ 12.85 Lakhs INR | 2016–2018 | |
| 15. | Foundation for Geriatric Diseases at KI | Principal Investigator | 475000 SEK ~ 40.5 Lakhs INR | 2016–2019 | |
| 16. | Loo and Hans Ostermans foundation for medical research in geriatrics | Principal Investigator | 50000 SEK ~ 4.3 Lakhs INR | 2018 |
Travel Grants
| S.NO. | Funding Agency | Event | Amount |
|---|---|---|---|
| 1. | Wenner-Gren Foundation Travel Award, Stockholm, Sweden | 11th Clinical Trials on Alzheimer’s Disease (CTAD2018), Barcelona, Spain, Oct 24–27, 2018 | 8,000 kr |
| 2. | Karolinska Institutet Travel Award, Stockholm, Sweden | 253rd American Chemical Society National Meeting & Exposition, San Francisco, USA, Apr 2–6, 2017 | 10,500 kr |
| 3. | European Union Horizon 2020 Travel Fund | Frontiers in Medicinal Chemistry 2020, Berlin, Germany, Mar 10–14, 2020 | 12,000 EUR |
| 4. | Wenner-Gren Foundation Travel Award, Stockholm, Sweden | 14th International Athens / Springfield Symposium on Advances in Alzheimer Therapy, Athens, Greece, Mar 09–12, 2016 | 8,000 kr |
| 5. | Karolinska Institutet Travel Award, Stockholm, Sweden | 249th American Chemical Society National Meeting & Exposition, Denver, USA, Mar 22–26, 2015 | 6,700 kr |
| 6. | Young Scientist Travel Award by Indian Council of Medical Research | 12th International Chemistry Conference Africa, University of Pretoria, South Africa, Jul 8–12, 2013 | 81000 INR |
Research Students (Ph.D. + Master Thesis)
| Serial No. | Program | Candidate / Student | Research Interest | Current Status | Contact |
|---|---|---|---|---|---|
| Ph.D. Candidates | |||||
| 1. | Ph.D. | Chokhat Diksha Rajebhau | Design, Synthesis and Biological Evaluation of Novel Therapeutics as Protein Aggregation modulators for Alzheimer's Disease | Ongoing | cdiksharajebhau.rs.phe25@itbhu.ac.in |
| 2. | Ph.D. | Pradeep Uttamchand Yadav | AI-enabled Discovery of Novel Polymerase Theta Inhibitors | Ongoing | pradeepuyadav.rs.phe25@itbhu.ac.in |
| 3. | Ph.D. | Gauri Mishra | AI-enabled Discovery of Novel Polymerase Theta Inhibitors | Ongoing | gaurimishra.rs.phe25@itbhu.ac.in |
| 4. | Ph.D. | Ninave Raju Prakash | Structure Based Discovery of novel bacterial topoisomerase inhibitors | Ongoing | ninaverajuprakash.rs.phe25@itbhu.ac.in |
| 5. | Ph.D. | Harikesh Kumar Gupta | Design, Synthesis and Biological Evaluation of dual protein aggregation modulators for the treatment of Alzheimer's Disease | Ongoing | harikeshkumargupta.rs.phe25@itbhu.ac.in |
| 6. | Ph.D. | Jatin Jangra | Design, Discovery and Development of Protein aggregation modulators for the treatment of neurodegeneration. | Ongoing | jatin.rs.phe24@iitbhu.ac.in |
| 7. | Ph.D. | Anurag TK Baidya | Design, synthesis and evaluation of novel Choline AcetylTransferase ligands for neurodegenerative diseases. | Awarded (2025) | anuragtkbaidya.rs.phe20@itbhu.ac.in |
| 8. | Ph.D. | Bhanuranjan Das | Design, Synthesis, and Biological Evaluation of Novel Protein Aggregation Modulators as Potential Therapeutics Against Alzheimer’s Disease. | Awarded (2024) | bhanuranjadas.rs.phe20@itbhu.ac.in |
| Master Thesis Students (M.Pharm / M.Tech / IDD) | |||||
| 1. | M.Pharm | Isha Mahindru | Design, Discovery and Development of Protein aggregation modulators for the treatment of neurodegeneration. | M.Pharm (2024–2026) | isha.phe24@itbhu.ac.in |
| 2. | M.Pharm | Vineet Kumar | Structure Based Discovery of novel bacterial topoisomerase inhibitors | M.Pharm (2024–2026) | vineetkumar.phe24@itbhu.ac.in |
| 3. | M.Pharm | Vishwakarma Krishna Ramesh | Design, Synthesis and Biological Evaluation of dual protein aggregation modulators for the treatment of Alzheimer's Disease | M.Pharm (2024–2026) | vishwakarmakramesh.phe24@itbhu.ac.in |
| 4. | IDD | Vishisht Dubey | De novo design of novel polymerase theta inhibitors | IDD (2021–2026) | vishisht.dubey.phe21@itbhu.ac.in |
| 5. | IDD | Devansh Jain | Discovery of novel PROTAC degraders using Generative AI | IDD (2021–2026) | devansh.jain.phe21@itbhu.ac.in |
| 6. | M.Pharm | Alisha Shaikh | Computational Design and Modeling of PROTAC Molecules for Targeted Protein Degradation | M.Pharm (2023–2025) | alishasshaikh.phe23@itbhu.ac.in |
| 7. | IDD | Samruddhi Harichandra Dhanwate | DL Based BBB permeability prediction | IDD (2020–2025) | samruddhi.hdhanwate.phe20@itbhu.ac.in |
| 8. | M.Pharm | Abhinetra J. Bhopale | Design, Synthesis and In silico Evaluation of Novel Allosteric Modulators of Cannabinoid Receptor 1 | M.Pharm (2022–2024) | abhinetrajbhopale.phe22@itbhu.ac.in |
| 9. | M.Pharm | Sourabh Chakrabarti | Machine Learning Assisted Discovery of Potential Cyclin-Dependent Kinase 5 Inhibitors | M.Pharm (2022–2024) | sourabhchakrabarti.phe22@itbhu.ac.in |
| 10 | IDD | Akash Kumar Verma | De Novo Design of Novel CB1R Ligands Using Generative AI | IDD (2019–2024) | akashkr.verma.phe19@iitbhu.ac.in |
| 11 | M.Pharm | Rampa Rahul Salmon | Conformational Changes in Human RXRgamma Protein Using Molecular Dynamics Simulations | M.Pharm (2021–2023) | ramparahulsalmon.phe21@itbhu.ac.in |
| 12 | IDD | Abhinav Kumar Goswami | Deep Learning Based Virtual Screening for Identification of Potential Choline Acetyltransferase Inhibitors | IDD (2018–2023) | abhinav.ksharma.phe22@itbhu.ac.in |
| 12 | M.Pharm | Alen T. Mathew | Effects of Post Translational Modifications on Human Tau Protein Dynamics using simulations | M.Pharm (2020–2022) | alentmathew.phe20@iitbhu.ac.in |
| 14 | IDD | Gokul S. Pradeep | Brain tumor classification using machine learning | IDD (2017–2022) | gokuls.pradeep.phe17@itbhu.ac.in |
| 15 | M.Pharm | Bharti | Structural requirements for prediction of inhibitory activity for AChE inhibitors through Monte Carlo based QSAR | M.Pharm (2019–2021) | bharti.phe19@itbhu.ac.in |
List of Publications
(Research papers, patent, book chapters, PDB deposition, and presentations)
Please visit the Google Scholar webpage for an updated list of publications.
View Google Scholar Profile and List of Publications
Patent application
- UK patent application (24 March, 2017, KARBX/P60707GB)
PDB depositions
- 5NJX: Human FKBP51 protein in complex with C-terminal peptide of Human HSP 90-alpha, DOI: 10.2210/pdb5njx/pdb
- 5OMP: Human FKBP5 protein, DOI: 10.2210/pdb5omp/pdb
For prospective postdocs
- If you are motivated researcher with a PhD degree in medicinal chemistry or related field, keep an eye on this page for a vacancy. You are welcome to apply for your own postdoctoral fellowship such as NPDF. A highly useful database of research funding opportunities hosted by NCBS, TIFR can be found here.
For prospective PhD
- PhD admissions are made twice in a year on institute sponsored seat and detailed information can be found at this link. Candidates having their own fellowships such as CSIR SRF, ICMR SRF, DST Inspire, RGNF etc. are encouraged to apply.
For internships
- If you are looking forward to a 2-3 months internship in the field of computational drug design/ medicinal chemistry, do not hesitate to email me for an informal inquiry.