Abstract
Metabolic syndrome (MetS) is a highly prevalent disease cluster worldwide. It requires polypharmacological treatment of the single conditions including type II diabetes, hypertension, and dyslipidemia, as well as the associated comorbidities. The complex treatment regimens with various drugs lead to drug-drug interactions and inadequate patient adherence, resulting in poor management of the disease. Multi-target approaches aim at reducing the polypharmacology and improving the efficacy. This review summarizes the medicinal chemistry efforts to develop multi-target ligands for MetS. Different combinations of pharmacological targets in context of in vivo efficacy and future perspective for multi-target drugs in MetS are discussed.
Highlights
Metabolic diseases are becoming increasingly prevalent and have a major impact on public health worldwide (Kahn et al, 2005; Potenza and Mechanick, 2009; Shaw et al, 2010)
Insulin resistance is a key component for metabolic syndrome (MetS) and metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD)
This study demonstrated that natural (bile acid: Chenodeoxycholic acid (CDCA)) as well as synthetic (GW4064) farnesoid X receptor (FXR) ligands induce the expression of peroxisome proliferator-activated receptor-γ (PPARγ) in hepatic stellate cells (HSCs)
Summary
Metabolic diseases are becoming increasingly prevalent and have a major impact on public health worldwide (Kahn et al, 2005; Potenza and Mechanick, 2009; Shaw et al, 2010). A large portion of patients with NAFLD display typical features of MetS including abdominal obesity, dyslipidemia, hypertension, insulin resistance, or type 2 diabetes (Chalasani et al, 2012; El-Kader and El-; El-Kader and El-Den Ashmawy, 2015). Due to the complex pathophysiology, the current therapeutic approaches to treat MetS, type 2 diabetes, and NAFLD need multiple treatments regulating lipid and glucose homeostasis as well as blood pressure control (Grundy et al, 2005; Grundy, 2006; Oseini and Sanyal, 2017; Sumida and Yoneda, 2018)
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