The Kotra group is a multi-disciplinary group adapting an integrated approach in drug discovery that combines advanced principles in computer modeling, medicinal chemistry and biochemistry for efficient drug discovery process. Interests of the group lie in understanding enzyme/receptor structures; identifying underlying principles in the disease process; designing molecular intervention strategies using synthetic medicinal chemistry; confirming the biological/therapeutic activities of the designed compounds; and performing animal efficacy studies using disease models. Our group collaborates extensively with molecular biologists, structural biologists and clinician-scientists around the globe. Chemistry is at the core of all our research programs.
Lakshmi P Kotra
- Research projectsThe Kotra group currently has a number of exciting ongoing drug discovery projects. These include structure-based design of (1) inhibitors against orotidine monophosphate decarboxylase (ODCase), (2) drugs effective for the treatment of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease, (3) interferon mimetics as broad-spectrum antivirals, (4) drugs targeting thrombocytopenia and (5) antimalarials. Students and staff conduct chemical, biochemical and animal studies, as well as drug formulations experiments to translate discoveries into medicines. Research in the Kotra group is funded through a variety of public and private sector grants and contracts.
- Core technical expertiseThe Kotra group has technical competency/expertise in synthetic medicinal chemistry, computational chemistry and biochemical and animal studies, spanning small molecule therapeutics as well as biologics. Designing new strategies, especially in small molecule drug discovery, is a unique and special strength in the group.
- Kotra group accomplishmentsThe Kotra group has made significant contributions in medicinal chemistry and drug discovery leading to a number of licenses and translation into preclinical development. These include three novel classes of antimalarials, drugs for the treatment of diabetic neuropathy, pre-lead compounds targeting neurodegeneration in multiple sclerosis (MS), and functionally effective agonists to interferon receptor as potential antiviral agents. Group activities have produced several license agreements with private sector partners, including three start-up companies.
Surfactant protein D regulates caspase-8-mediated cascade of the intrinsic pathway of apoptosis while promoting bleb formation.
Mol Immunol. 2017 Dec;92:190-198
Cannabis Cannabinoid Res. 2017;2(1):274-281
Non-Covalent Protein Arginine Deiminase (PAD) Inhibitors Are Efficacious in Animal Models of Multiple Sclerosis.
J Med Chem. 2017 Oct 18;:
Bioorg Med Chem. 2017 Sep 05;:
A Conserved Residue, Tyrosine (Y) 84, in H5N1 Influenza A Virus NS1 Regulates IFN Signaling Responses to Enhance Viral Infection.
Viruses. 2017 May 12;9(5):
Ultraviolet irradiation increases green fluorescence of dihydrorhodamine (DHR) 123: false-positive results for reactive oxygen species generation.
Pharmacol Res Perspect. 2017 Apr;5(2):e00303
Inhibitors of protein arginine deiminases and their efficacy in animal models of multiple sclerosis.
Bioorg Med Chem. 2017 Mar 06;:
Apoptosis. 2017 Feb 06;:
Autoimmun Rev. 2016 Jun 11;
J Interferon Cytokine Res. 2015 Dec 24;
Senior Scientist, Toronto General Hospital Research Institute (TGHRI)
Director, Center for Molecular Design and Preformulations, UHN
Associate Professor, Leslie Dan Faculty of Pharmacy, University of Toronto
Scientific Director (Toronto-based), UHN-Shanghai