Target Development Service of HMG-CoA Reductase Inhibitors

HMG-CoA reductase inhibitors are remarkably safe and efficient medications that are the mainstay of hypercholesterolemia treatment and have proven to be an invaluable therapeutic strategy for non-alcoholic steatohepatitis (NASH). In order to provide the best and efficient service for our worldwide customers, Creative Biolabs has built a full range of platforms (Drug discovery, Hit identification, Hit to Lead, Target Identification and Validation, Lead Optimization) for small molecule drugs/antibody development to benefit the discovery of new therapies towards different diseases. Aided by our advanced platforms, we have developed a diversiform portfolio of targets and therapeutic strategies for NASH.

Introduction of HMG-CoA Reductase Inhibitors

HMG-CoA reductase inhibitors (also known as statins) are a class of lipid-lowering medications that can block the enzyme activity of HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase). HMG-CoA reductase (HMG-R) is involved in the synthesis of mevalonate, a naturally occurring substance that is used by the body to produce sterols, including cholesterol. HMG-CoA reductase inhibitors have been applied to efficient medications, such as pravastatin, fluvastatin, atorvastatin, simvastatin, and rosuvastatin. They are the mainstay of therapy for elevated low-density lipoprotein (LDL) cholesterol and both primary and secondary prevention of acute cardiovascular events and stroke. Multiple clinical trials have shown a mortality benefit with statin therapy in various populations.

Fig.1 Statins in pre-clinical research.

HMG-CoA Reductase Inhibitors for the Treatment of NASH

NASH is a non-alcoholic fatty liver disease, characterized by inflammation and fibrosis. Physiologically, NASH is associated with increased accumulation of both hepatic triglycerides and free cholesterol, and elevated free cholesterol is closely associated with increased expression of HMG-R. HMG-CoA reductase inhibitors can block the committed step in cholesterol biosynthesis, showing constant values in the nanomolar range, that effectively lower serum cholesterol levels and are evaluated in NASH treatment. In addition, HMG-CoA reductase inhibitors can decrease LDL-cholesterol production, and increase the number of LDL receptors on liver cells, which enhance the uptake and breakdown of LDL-cholesterol. Data suggest that statin treatment has a protective effect on the management of dyslipidemia in patients with NASH and improves the adverse outcomes of other conditions commonly associated with NASH (e.g. hyperlipidemia, diabetes mellitus, metabolic syndrome).

Fig.2 Current and emerging drugs for non-alcoholic fatty liver disease and their mechanism of action. (Eshraghian, 2017)

With advanced technologies and professional team, Creative Biolabs is devoted to finding more effective pharmaceutical candidates and therapies for NASH. At present, we can provide various HMG-CoA reductase inhibitors and other useful targets for NASH treatment. In addition, we can offer fully customized design services to meet every specific demand. Our NASH services include but not limited to:

• Biomarkers for NASH Diagnosis
• Target Discovery and Therapeutic Strategies
• Preclinical Models of NASH

If you have any other requests for NASH services, please feel free to contact us or directly send us a quote.

Reference

1. Eshraghian, A. Current and emerging pharmacological therapy for non-alcoholic fatty liver disease. World journal of gastroenterology. 2017, 23(42): 7495.