Emerging Therapies for Dyslipidemia: Known Knowns and Known Unknowns of MTP Inhibitors

Saurin      K. Raval; Preeti      S. Raval; Mukul      R. Jain

Abstract

Last decade had witnessed enormous efforts to develop therapies to treat one or more components of metabolic syndrome, a cluster of diseases including diabetes, obesity and dyslipidemia. Several newer targets are identified and evaluated to treat these metabolic disorders. Microsomal triglyceride transfer protein (MTP) has been identified as one of the promising target for the treatment of dyslipidemia. MTP plays crucial role in the assembly of triglyceride rich chylomicrones in enterocytes and VLDL in hepatocytes and several lines of evidence suggested that MTP inhibitors can be instrumental in combating familial hypercholesterolemia. Several first generation compounds are currently being evaluated in clinic and fatty liver is found to be the main adverse effect of these agents. Recently development of enterocyte specific inhibitor of MTP is emphasized in order to deal with fatty liver issue. In this review, we have dealt with important mechanistic aspects of MTP inhibition, patent scenario and clinical trial outcomes and some of the recent patents related to newly discover chemical scaffolds.

Keywords: Abetalipoproteinemia, familial hypercholesterolemia, metabolic syndrome, microsomal triglyceride transfer protein inhibitors, MTP inhibitors, STATINS, PPAR AGONISTS, NIACIN, BILE ACID SEQUESTRANTS, hypercholesterolemia