Emerging therapies for dyslipidemia: known knowns and known unknowns of MTP inhibitors.
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.
Zydus Research Centre, Sarkhej- Bavla N. H.8A, Moraiya, Ahmedabad- 382210, India. saurinraval@zyduscadila.com
Saurin K
SK
Raval
Preeti S
PS
Raval
Mukul R
MR
Jain
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D016896:Treatment Outcome
D002352:Carrier Proteins; D000960:Hypolipidemic Agents; C106092:microsomal triglyceride transfer protein