Research Topics
The SMC lab's interests lie in developing novel chemical probes and pharmacological tools to study the endocannabinoid system drug targets. Our focus is to design and develop novel small molecules with druggable properties for treatment of multi-factorial and hetero-etiological diseases like metabolic syndrome, pain and substance overuse disorders. The laboratory aims to exploit and maximize the therapeutic potential of the endocannabinoid system central and peripheral receptors with unique small molecule-based approaches. We use unified approaches, including medicinal chemistry, synthetic methodology development, analytical/bioanalytical chemistry, structural biology and computational chemistry to impact and refine our drug-discovery processes. One area of research is focused on synthesizing and studying novel 'four-arm' CB1 modulators with altered functional profiles in the context of biased and allosteric signaling. With regard to drug-design, the CB1 blockers (MRI-1867 and MRI-1891) generated are currently in clinical trials for treating fibrotic and metabolic disorders. Further we have now developed a new platform for developing 'tailored/designed polypharmacology' to deliver focused multi-target therapeutics for ameliorating alcohol associated diseases. An additional thrust in our laboratory is to advance new synthetic methodologies that will allow the expeditious assembly of novel chemical entities (NCEs) as well as targeted small-molecule libraries. On this front, we aim to utilize under-explored elements to drive molecular design. Together, our work has vast implications for delivering therapies based on precision chemo/pharmacology paradigm, particularly for diseases states which have limited treatment options.
Biography
Dr. Iyer earned a Ph.D. degree in Chemistry from the Pennsylvania State University. Prior to that, she obtained her Master of Science degree in Organic Chemistry from the Indian Institute of Technology, Bombay (Mumbai) India. She trained as a postdoctoral fellow with Dr. Kenner Rice at NIDA studying the medicinal chemistry of opioid receptors and sigma receptors in substance use disorders towards developing non-addicting pharmacotherapies. After a research fellowship with Dr. George Kunos at NIAAA, she led a Medicinal Chemistry Core Program at NIAAA to develop translational approaches targeting the peripheral CB1 receptors. In 2021 she established an independent research program at NIAAA, Division of Clinical and Biological Research (DICBR) where she is the principal investigator and acting chief of Section on Medicinal Chemistry.
Selected Publications
- Dvorácskó S, Herrerias A, Oliverio A, Bhattacharjee P, Pommerolle L, Liu Z, Feng D, Lee YS, Hassan SA, Godlewski G, Cinar R, Iyer MR. Cannabinoformins: Designing Biguanide-Embedded, Orally Available, Peripherally Selective Cannabinoid-1 Receptor Antagonists for Metabolic Syndrome Disorders. J Med Chem. 2023.
- Iyer MR, Cinar R, Wood CM, Zawatsky CN, Coffey NJ, Kim KA, Liu Z, Katz A, Abdalla J, Hassan SA, Lee YS. Synthesis, Biological Evaluation, and Molecular Modeling Studies of 3,4-Diarylpyrazoline Series of Compounds as Potent, Nonbrain Penetrant Antagonists of Cannabinoid-1 (CB(1)R) Receptor with Reduced Lipophilicity. J Med Chem. 2022;65(3):2374-2387.
- Liu Z, Iyer MR, Godlewski G, Jourdan T, Liu J, Coffey NJ, Zawatsky CN, Puhl HL, Wess J, Meister J, Liow JS, Innis RB, Hassan SA, Lee YS, Kunos G, Cinar R. Functional Selectivity of a Biased Cannabinoid-1 Receptor (CB(1)R) Antagonist. ACS Pharmacol Transl Sci. 2021;4(3):1175-1187.
- Yeliseev A, Iyer MR, Joseph TT, Coffey NJ, Cinar R, Zoubak L, Kunos G, Gawrisch K. Cholesterol as a modulator of cannabinoid receptor CB(2) signaling. Sci Rep. 2021;11(1):3706.
- Iyer MR, Kundu B, Wood CM. Soluble epoxide hydrolase inhibitors: an overview and patent review from the last decade. Expert Opin Ther Pat. 2022;32(6):629-647.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
View additional Principal Investigators in Molecular Biology and Biochemistry
This page was last updated on Thursday, August 31, 2023