RESAT CINAR, BPharm, PhD, MBA

I am a pharmacist and pharmacologist with 20 years of research, leadership, project management experiences in basic and translational sciences, and drug discovery projects with translational success spanning from disease mechanisms, therapeutic target identification, drug design, preclinical development, therapeutic candidate selection for diverse spectrum of metabolic and fibrotic diseases such as obesity, diabetes, and organ fibrosis including liver, skin, kidney, and lung (Hermansky-Pudlak syndrome pulmonary fibrosis, idiopathic pulmonary fibrosis). I lead a research team at NIH. We use multi-disciplinary approaches and cutting edge technologies with integration of experimental and translational models in highly collaborative environment to achieve a systems level understanding of complex metabolic and fibrotic processes to identify biomarkers and effective therapeutic targets. My focus is pursuing a multi-target therapeutic approach to improve treatment efficacy by simultaneously engaging multiple pathogenic pathways in complex metabolic and fibrotic disorders. I am an internationally known expert in cannabinoid receptors pharmacology and its role in metabolic and fibrotic disorders. I am an author over 90 published research studies explored roles of endocannabinoids and cannabinoid receptors in metabolic regulations. These studies identified peripheral CB1R antagonism as a therapeutic target in metabolic and fibrotic disorders. We demonstrated multi-targeting and/or functional selectivity as an emerging strategy to develop more efficient and safer therapeutic modalities for peripheral CB1R antagonism. We identified dual inhibition of CB1R and iNOS as a more effective antifibrotic strategy in multiple fibrotic disorders including fibrosing rare lung diseases. I am involved in the preclinical development, patenting and lead candidate selection of novel peripherally acting hybrid compounds (CB1R/iNOS or CB1R/AMPK) as next generation CB1R antagonists. We uncovered distinct signaling activation of CB1R in insulin resistance. Then we introduced the first in-class functionally biased peripheral CB1R antagonist MRI-1891 (monlunabant) with therapeutic potential in diabetes and metabolic disorders with improved safety and efficacy through functional selectivity of CB1R antagonism. We discovered two novel therapeutic candidates MRI-1867 (zevaquenabant) and MRI-1891 (monlunabant), which are translated into clinic. After successful completion of Phase 1B and 2A trials, monlunabant has been further investigated in clinical trials for metabolic disorders.