Umesh Prasad Singh , Ph.D. ( IISc, Bengaluru)

Senior Principal Scientist and Head, Infectious Diseases & Immunology Division
Infectious Diseases and Immunology
details-banner

Research Focus

Drug Discovery (anti-viral for dengue and SARS-Cov2), Computational Chemistry, Molecular modeling, Structural Biology, Structural Chemistry (non-coded amino acid based peptides)

Research Interest

Discovery scientist in preclinical translational research for about 20 years

Drug Discovery achievements:

  • Part of the discovery team that characterized atomic resolution structure of the ribonuclease ONCONASE. As part of the confirmatory stage of phase III, the U.S. Food and Drug Administration (FDA) has given Onconase orphan and fast-track drug status for Malignant Pleural Mesothelioma.
  • Part of the innovation teams that innovated the molecule Licogliflozin, which is currently in human clinical trials (Phase-II) for Diabetes Mellitus-2.
  • Part of the innovation teams that innovated the molecule GKM-001, which successfully completed Phase-Ib clinical trials and is about to enter Phase II for Diabetes Mellitus-2.
  • Part of innovation teams that have innovated selective JAK kinases (for RA, SLE and other autoimmune and inflammatory diseases), BTK kinases (for MCL, CLL and RA etc.) and FAAH inhibitors as potent antinociceptive therapeutic agents. 

Translational Drug discovery - areas of experience (mainly industry based): 

  • Translation Drug discovery areas: Present focus is mainly Infectious viral diseases like dengue and SARS-Cov2. Earlier experience (mainly industry based): Metabolic diseases (Diabetes, Asthma, allergy, COPD, IBD), Alzheimer’s, Pain/Inflammation, and ribonuclease based protein cancer-therapeutics
  • Drug targets like viral proteases, GPCRs, Kinases, solute transporter(s), and their role in different diseases, solving problems of developing therapeutics through understanding molecular mechanisms
  • Structure/ligand based drug design, Protein homology modeling, Molecular modeling of proteins/ protein-drug complexes, High Throughput Virtual Screening (HTVS), Pharmacophore based modeling, molecular docking, molecular dynamics, compound database management
  • Protein-based activity assays, biophysical assays
  • X-ray crystallographic studies of proteins, peptides, protein-ligand complexes
  • Design of novel non-coded amino acid based peptides, peptide-based inhibitors as anti-viral agents
  • Natural product discovery for therapeutic applications (anti-viral and anti-cancer)

 

Credentials

Ph.D, Science (Structural Biology/ Biophysics), Indian Institute of Science (IISc), Bangalore [1997 – 2004].

MSc (Research), Interdisciplinary (physics & Chemistry), Institute of Chemical Technology (ICT) Mumbai [1993 – 1996]. 

BSc, Physics (Major), Chemistry and Mathematics, DG Ruparel College, University of Mumbai [1989 – 1992].

 

Patents & Publications

Academic Publications:

  1. Chaudhary, S.; Rai, R. N.; Jyothi, D.; Singh, U. P.; Kumar, A. Solid-State Green Synthesis of Two (1:1) Organic Intermolecular Compounds; Their Physico-Chemical, Thermal, Single Crystal Growth, and Atomic Packing Studies. Mater. Chem. Phys. 2024, 322, 129541. https://doi.org/10.1016/J.MATCHEMPHYS.2024.129541.
  2. Chatterjee, A.; Roy, T.; Jyothi, D.; Mishra, V. K.; Singh, U. P.; Swarnakar, S. Melatonin Inhibits AGS Cell Proliferation by Binding to the ATP Binding Site of CDK2 Under Hyperglycemic Conditions. Cell Biochem. Biophys. 2024, 82 (2), 895–908. https://doi.org/10.1007/S12013-024-01241-9.
  3. Pal, P. C.; Nag, S.; Jyothi, D.; Das, S.; Saha, K. Das; Singh, U. P. Swietenolide Isolated from Swietenia Macrophylla King in Hook Seeds Shows in Vitro Anti-Colorectal Cancer Activity through Inhibition of Mouse Double Minute 2 (MDM2) Homolog. Nat. Prod. Res. 2024, 38 (12), 2097–2104. https://doi.org/10.1080/14786419.2023.2233045.
  4. Mani, S.; Kaur, A.; Jakhar, K.; Kumari, G.; Sonar, S.; Kumar, A.; Das, S.; Kumar, S.; Kumar, V.; Kundu, R.; Pandey, A. K.; Singh, U. P.; Majumdar, T. Targeting DPP4-RBD Interactions by Sitagliptin and Linagliptin Delivers a Potential Host-Directed Therapy against Pan-SARS-CoV-2 Infections. Int. J. Biol. Macromol. 2023, 245. https://doi.org/10.1016/J.IJBIOMAC.2023.125444.
  5. Chaudhary, S.; Rai, R. N.; Jyothi, D.; Singh, U. P. Solid State Synthesis, Thermal, Spectral, Optical, Crystal Structure and Atomic Packing Studies of 2-(3-Hydroxyphenyl)-2,3-Dihydroquinazolin-4(1H)-One. Mater. Lett. 2023, 341, 134253. https://doi.org/10.1016/J.MATLET.2023.134253.
  6. Koul, S.; Kurhade, S.; Bhosale, S.; Naik, K.; Salunkhe, V.; Ravula, S.; Punde, P.; Velayutham, R.; Tiwari, A.; Ahl, D.; Malkapuram, S.; Mudagala, V.; Raje, A.; Umrani, D.; Tambe, S.; Patil, P.; Singh, U.; Bhuniya, D.; Hariharan, N.; Mookhtiar, K. Design and Synthesis of Novel Spirocyclic Carboxylic Acids as Potent and Orally Bioavailable DGAT1 Inhibitors and Their Biological Evaluation. Bioorganic Med. Chem. Lett. 2022, 62. https://doi.org/10.1016/j.bmcl.2022.128632.
  7. Shankar, S.; Jyothi, D.; Rahim, J. ur; Pal, P. C.; Singh, U. P.; Rai, R. Conformation of Achiral α/β Hybrid Peptides Containing Glycine and 1-Aminocyclohexaneacetic Acid. ChemistrySelect 2022, 7 (10), 1–7. https://doi.org/10.1002/slct.202104453.
  8. Das, R.; Kar, S.; Biswas, S.; Singh, U. P.; Banerjee, E. R. Therapeutic Effect of Combinatorial Probiotics to Protect Intestinal Barrier Function. EC Microbiol. 2017, 9.2, 84–95.
  9. Yadav, D. K.; Bharitkar, Y. P.; Hazra, A.; Pal, U.; Verma, S.; Jana, S.; Singh, U. P.; Maiti, N. C.; Mondal, N. B.; Swarnakar, S. Tamarixetin 3-O-β- d -Glucopyranoside from Azadirachta Indica Leaves: Gastroprotective Role through Inhibition of Matrix Metalloproteinase-9 Activity in Mice. J. Nat. Prod. 2017, 80 (5). https://doi.org/10.1021/acs.jnatprod.6b00957.
  10. Wani, N. A.; Raghothama, S.; Singh, U. P.; Rai, R. C11 /C9 Helical Folding in Αβ Hybrid Peptides Containing 1-Amino-Cyclohexane Acetic Acid (Β3, 3 -Ac6 C). Chemistry 2017, 23 (35), 8364–8370. https://doi.org/10.1002/CHEM.201700265.
  11. Shankar, S.; Ahmad Wani, N.; Prasad Singh, U.; Rai, R.; Wani, N. A.; Rai, R.; Shankar, S.; Singh, U. P. Incipient Twisted Ribbon Structure Stabilized by C12 Helical Turns in Γ4/α Hybrid Peptide. ChemistrySelect 2016, 1 (13), 3675–3678. https://doi.org/10.1002/SLCT.201600793.
  12. Wani, N. A.; Gupta, V. K.; Singh, U. P.; Aravinda, S.; Rai, R. Folded Structure Stabilized by C7, C10 and C12 Hydrogen Bonds in Αγ Hybrid Peptides. ChemistrySelect 2016, 1 (8), 1674–1677. https://doi.org/10.1002/SLCT.201600389.
  13. Das, R.; Paul, P.; Mukherjee, K.; Mitra, S.; Singh, U. P.; Banerjee, E. R. Anti-Oxiflammatory Profile of Date Extracts (Phoenix Sylvestris). Biomed. Res. Ther. 2015. https://doi.org/10.15419/bmrat.v2i06.53.
  14. Das, R.; Mitra, S. ; Mukherjee, K.; Paul, P.; Singh, U. P.; Ray Banerjee, E. Anti-Oxidant and Anti-Inflammatory Activities of Different Varieties of Piper Leaf Extracts (Piper Betle L.). J. Nutr. Food Sci. 2015, 5 (5). https://doi.org/10.4172/2155-9600.1000415.
  15. Barawkar, D. A.; Bandyopadhyay, A.; Deshpande, A.; Koul, S.; Kandalkar, S.; Patil, P.; Khose, G.; Vyas, S.; Mone, M.; Bhosale, S.; Singh, U.; De, S.; Meru, A.; Gundu, J.; Chugh, A.; Palle, V. P.; Mookhtiar, K. A.; Vacca, J. P.; Chakravarty, P. K.; Nargund, R. P.; Wright, S. D.; Roy, S.; Graziano, M. P.; Cully, D.; Cai, T. Q.; Singh, S. B. Discovery of Pyrazole Carboxylic Acids as Potent Inhibitors of Rat Long Chain L-2-Hydroxy Acid Oxidase. Bioorganic Med. Chem. Lett. 2012, 22 (13), 4341–4347. https://doi.org/10.1016/j.bmcl.2012.05.020.
  16. Basu, S.; Prasad, U. V.; Barawkar, D. A.; De, S.; Palle, V. P.; Menon, S.; Patel, M.; Thorat, S.; Singh, U. P.; Sarma, K. Das; Waman, Y.; Niranjan, S.; Pathade, V.; Gaur, A.; Reddy, S.; Ansari, S. Discovery of Novel and Potent Heterocyclic Carboxylic Acid Derivatives as Protein Tyrosine Phosphatase 1B Inhibitors. Bioorganic Med. Chem. Lett. 2012, 22 (8), 2843–2849. https://doi.org/10.1016/j.bmcl.2012.02.070.
  17. Barawkar, D. A.; Meru, A.; Bandyopadhyay, A.; Banerjee, A.; Deshpande, A. M.; Athare, C.; Koduru, C.; Khose, G.; Gundu, J.; Mahajan, K.; Patil, P.; Kandalkar, S. R.; Niranjan, S.; Bhosale, S.; De, S.; Mukhopadhyay, S.; Chaudhary, S.; Koul, S.; Singh, U.; Chugh, A.; Palle, V. P.; Mookhtiar, K. A.; Vacca, J.; Chakravarty, P. K.; Nargund, R. P.; Wright, S. D.; Roy, S.; Graziano, M. P.; Singh, S. B.; Cully, D.; Cai, T. Q. Potent and Selective Inhibitors of Long Chain L-2-Hydroxy Acid Oxidase Reduced Blood Pressure in DOCA Salt-Treated Rats. ACS Med. Chem. Lett. 2011, 2 (12), 919–923. https://doi.org/10.1021/ml2001938.
  18. Holloway, D. E.; Singh, U. P.; Shogen, K.; Acharya, K. R. Crystal Structure of Onconase at 1.1 Å Resolution - Insights into Substrate Binding and Collective Motion. FEBS J. 2011, 278 (21). https://doi.org/10.1111/j.1742-4658.2011.08320.x.
  19. Singh, U. P. Structure of a Cyclic Water Tetramer in a Nucleotide Crystal Host and a Hypothetical Model for Water Cluster Growth. J. Mol. Struct. 2010, 983 (1–3). https://doi.org/10.1016/j.molstruc.2010.08.034.
  20. Singh, U. P.; Ardelt, W.; Saxena, S. K.; Holloway, D. E.; Vidunas, E.; Lee, H.-S.; Saxena, A.; Shogen, K.; Acharya, K. R. Enzymatic and Structural Characterisation of Amphinase, a Novel Cytotoxic Ribonuclease from Rana Pipiens Oocytes. J. Mol. Biol. 2007, 371 (1). https://doi.org/10.1016/j.jmb.2007.04.071.
  21. Deshpande, V. D.; Singh, U. Correlating Miscibility of PVC/PMMA Blend with Polymer Chain Orientation. J. Appl. Polym. Sci. 2006. https://doi.org/10.1002/app.23322.
  22. Singh, U. P.; Thomas, M.; Seshadri, T. P.; Bhattacharya, S. Ethyl 2-[/V-(Ferf-Butyloxycarbonyl)-L-Alanylamino]-4-Methyl-1,3-Thiazole-5-Carboxylate Reveals a Trans Orientation of the Preceding Amide N - H with Respect to the Thiazole-Ring Sulfur. Acta Crystallogr. Sect. C Cryst. Struct. Commun. 2000, 56 (12). https://doi.org/10.1107/S0108270100012439.

 

Patents:

  1. Substituted fused tricyclic compounds, compositions and medicinal applications thereof; Barawkar, Dinesh; Bende, Tanushree; Zahler, Robert; Bandyopadhyay, Anish; Sarangthem, Robindro Singh; Doshi, Jignesh; Waman, Yogesh; Jadhav, Rushikesh; Singh, Umesh Prasad; (2021), CA2830882C   https://patents.google.com/patent/CA2830882C/en
  2. Substituted fused tricyclic compounds, compositions and medicinal applications thereof; Barawkar, Dinesh; Bende, Tanushree; Zahler, Robert; Bandyopadhyay, Anish; Sarangthem, Robindro Singh; Doshi, Jignesh; Waman, Yogesh; Jadhav, Rushikesh; Singh, Umesh Prasad; (2018), JP6277121B2 https://patents.google.com/patent/JP6277121B2/en
  3. Substituted fused tricyclic compounds, compositions and medicinal applications thereof; Barawkar, Dinesh; Bende, Tanushree; Zahler, Robert; Bandyopadhyay, Anish; Sarangthem, Robindro Singh; Doshi, Jignesh; Waman, Yogesh; Jadhav, Rushikesh; Singh, Umesh Prasad; (2017), EP2688890B1 https://patents.google.com/patent/EP2688890B1/en
  4. Amide Compounds, Compositions and Applications Thereof; Kharul, Rajendra; Bhunia, Debnath; Mookhtiar, Kasim A.; Singh, Umesh; Hazare, Atul; Patil, Satish; Datarange, Laxmikant; Thakkar, Mahesh; (2017), ZA201402903B  https://patents.google.com/patent/ZA201402903B/en
  5. Amide Compounds, Compositions and Applications Thereof; Kharul, Kharul,Rajendra; Bhunia, Debnath; Mookhtiar, Kasim A.; Singh, Umesh; Hazare, Atul; Patil, Satish; Datarange, Laxmikant; Thakkar, Mahesh; (2017) US 9,682,953 B2  https://patents.google.com/patent/US9682953B2/en
  6. Amide Compounds, Compositions and Applications Thereof; Kharul, Kharul,Rajendra; Bhunia, Debnath; Mookhtiar, Kasim A.; Singh, Umesh; Hazare, Atul; Patil, Satish; Datarange, Laxmikant; Thakkar, Mahesh; (2016), AU2012311061B2 https://patents.google.com/patent/AU2012311061B2/en
  7. Substituted fused tricyclic compounds, compositions and medicinal applications thereof; Barawkar, Dinesh; Bende, Tanushree; Zahler, Robert; Bandyopadhyay, Anish; Sarangthem, Robindro Singh; Doshi, Jignesh; Waman, Yogesh; Jadhav, Rushikesh; Singh, Umesh Prasad; (2015), ZA201307819B  https://patents.google.com/patent/ZA201307819B/en
  8. Substituted fused tricyclic compounds, compositions and medicinal applications there of; Barawkar, Dinesh; Bende, Tanushree; Zahler, Robert; Bandyopadhyay, Anish; Sarangthem, Robindro Singh; Doshi, Jignesh; Waman, Yogesh; Jadhav, Rushikesh; Singh, Umesh Prasad; (2015), US9115133B2 https://patents.google.com/patent/US9115133B2/en
  9. Amide Compounds, Compositions and Applications Thereof; Kharul, Rajendra; Bhunia, Debnath; Mookhtiar, Kasim A.; Singh, Umesh; Hazare, Atul; Patil, Satish; Datarange, Laxmikant; Thakkar, Mahesh; (2014), JP2014527981A https://patents.google.com/patent/JP2014527981A/en
  10. Bicyclic compounds, Compositions and medicinal applications thereof Thakkar ,Mahesh; Koul, Summon; Bhuniya, Debnath, Singh, Umesh Prasad; (2013), WO2013/157021 A1  https://patents.google.com/patent/WO2013157021A1/en
  11. Amide Compounds, Compositions and Applications Thereof; Kharul, Rajendra; Bhunia, Debnath; Mookhtiar, Kasim A.; Singh, Umesh; Hazare, Atul; Patil, Satish; Datarange, Laxmikant; Thakkar, Mahesh; (2013), WO2013042139A1 https://patents.google.com/patent/WO2013042139A1/en
  12. Substituted fused tricyclic compounds, compositions and medicinal applications thereof; Barawkar, Dinesh; Bende, Tanushree; Zahler, Robert; Bandyopadhyay, Anish; Sarangthem, Robindro Singh; Doshi, Jignesh; Waman, Yogesh; Jadhav, Rushikesh; Singh, Umesh Prasad; (2012), WO2012127506A1 https://patents.google.com/patent/WO2012127506A1/en
➤