Santosh Khedkar, PhD
Successful researcher with track record of progressing discovery projects by applying computational modeling methods, as supported by patent applications. Recognized for excellence, integrity, proactivity, and commitment to manage team, projects & resources, along with entrepreneurial and leadership skills.
Skills
About
• Hit-to-lead, lead identification and optimization (LI/LO), candidate selection.
• Structure-based design, binding energy calculations, molecular dynamics (MD) simulations, pharmaco-phore mapping, substructure search, scaffold hopping, conformational analyses, molecular and macro-molecular (protein/DNA) docking, covalent docking, SB/LB-library screens (LI/LO), QM calculations.
• Modeling new drug modalities: PROTACs, Molecular-glues, ADCs, mRNA, covalent drugs; Allosteric Modulators, Macrocyclic compounds, Nucleic Acid (CDNs, aptamers)-based therapeutics, peptides.
• Successfully contributed to therapeutic areas encompassing but not limited to immuno-oncology (STING, Phase 1), ubiquitin proteasome system (UPS) pathway (molecular glue, PROTACs, IND/2021; patent), nuclear hormone receptor (VDR, patent), transcription factors (patent), tubulin binders (Plinabu-lin, Phase 3, NDA Priority Review; patent), anti-inflammatory program (PDE4, LO; patent), ADC program (unpublished), etc.
• Biologics: antibody & peptide modeling, protein docking, thermal stability, affinity maturation, ADC.
• Descriptor-based mathematical modeling (QSAR/QSPR) to build predictive/ statistical models.
• Proficiency in modeling suites: Schrodinger, AMBER, MOE, BioSolveIT.
• Data analytics and management tools: Canvas, KNIME, Vortex (Dotmatics), Spotfire, R, DataWarrior.
• Sound knowledge of medicinal chemistry concepts in addressing design challenges.
• Synthesis and purification of small organic molecules (early career pre-PhD 2+ yrs experience).
• Excellent written & oral communication, presentation and project management skills.
Work experience
Postdoctoral Research Fellow
Discovered non-steroidal agonists of vitamin D receptor (VDR); the lead compound inhibited cardiac hypertrophy in vitro and in vivo as compared to Calcitriol, an approved therapy in clinic, with significantly reduced calcemic effect (Patent WO2013009799 / US20140378507).
Identified inhibitors of Kruppel-like transcription factor (KLF10) – DNA interaction interface using virtual screening and structure-based lead optimization techniques (Patent US20170121318A1); received first prize for this research presented at BIDMC conference.
Elected to the editorial board of, and served as Guest Editor to special issue in, Curr. Top. Med. Chem.
Published 8 peer-reviewed articles and 2 patents during this period.
Senior Scientist
Successfully discovered inhibitors of (mRNA-cap binding) translation initiation factor, optimized tool compounds for target validation in collaboration with Drs. Nahum Sonenberg and Jerry Pelletier of McGill University, the pioneers of this protein pathway.
Established biologics (antibody) modeling platform to guide large-scale point-mutation screens aimed at enhancing thermal stability and binding affinity; predicted protein-antibody binding models (P:P docking).
Worked in collaboration with multi-disciplinary teams of medicinal/ organic chemists and biologists.
President and Chief Scientist
Founded ChemBio Discovery, Inc. as a Mass. corporation for scientific consulting & contract research, offering competitive computational chemistry services to support and drive preclinical drug discovery re-search of startups, small- and medium-size pharmaceutical and biotechnology companies.
Performed all aspects of business including successfully bringing projects of 20+ clients (~30 projects) to delivery of results and presentations; happy to share contacts of clients on request.
Established and managed High Performance Computing workstation with 50+ CPU cores & 2 GPUs running AMBER and Schrodinger packages in Linux and MacOS environments. Access to scalable cloud computing available through Amazon AWS to fulfill exponential on-demand needs.
Offering competitive & flexible long- & short-term engagement options to fulfill the needs of startups and small-to-medium size business.
