NASH Target Development Service for Glucagon-Like Peptide 1 (GLP-1) Agonists

Decreased secretion of glucagon-like peptide 1 (GLP-1) may contribute to the development of obesity which is a major risk factor for the development of type 2 diabetes mellitus (T2DM). In non-alcoholic fatty liver disease, liver fat (triglyceride) accumulation closely mirrors adipose tissue dysfunction and insulin resistance in obesity and T2DM. Therefore, Creative Biolabs is working on the development of GLP-1 agonists to provide a novel choice for the treatment of NASH. We provide our clients with products and custom services to better serve NASH drug development.

Introduction of Glucagon-Like Peptide 1 (GLP-1) Agonists

Glucagon-like peptide 1 (GLP-1) is a naturally occurring incretin hormone that is secreted from intestinal L-cells. GLP-1 can stimulate the pancreas to cause insulin (beta cells) proliferation and hold back glucagon release. Besides, GLP-1 interacts with GLP-1 receptor to exert a variety of biological functions, including delayed gastric emptying, appetite suppression, enhanced liver glucose uptake, and peripheral insulin sensitivity, as well as glucose-dependent insulin secretion. Native GLP-1 is considered to be a therapeutic method of type 2 diabetes (T2D) because of its attractive antidiabetic effects. In addition, GLP-1 can be rapidly degraded by dipeptidyl peptidase 4 (DPP-4), resulting in a very short half-life, which requires continuous infusion. Thus, pharmacological targets have focused on GLP-1 agonists that are resistant to degradation by DPP-4, and DPP-4 inhibitors that increase the half-life of native GLP-1. Due to their overall safety and efficacy, GLP-1 receptor agonists (GLP-1 RAs) are also becoming one of the cornerstones for the management of both obesity and type 2 diabetes mellitus (T2DM), and a novel alternative for the treatment of NASH.

Glucagon-Like Peptide 1 (GLP-1) Agonists for NASH Treatment

Non-alcoholic steatohepatitis (NASH) has emerged as one of the most common causes of chronic liver disease worldwide and T2D increases the risk of developing NASH, liver fibrosis, cirrhosis, and hepatocellular carcinoma. Studies have shown that GLP-1 agonists have a range of central nervous system and peripheral target tissues that can significantly affect liver metabolism. The pleiotropic effects of GLP-1 agonists have been shown to be effective in T2DM subjects, not only reducing hepatic steatosis and improving NAFLD and NASH, but also reducing plasma glucose and liver inflammation, improving cardiac function and preventing renal dysfunction. Moreover, although GLP-1RAs such as exenatide and liraglutide are mainly used in T2D, several studies have shown that they are also effective in patients with NASH. These beneficial effects include decreased serum alanine aminotransferase (ALT) levels, weight loss, and an improvement in hepatic fat content and fibrosis. These characteristics make GLP-1 agonists and GLP-1RAs potentially attractive to patients with NASH and metabolic syndrome.

Fig.2 Potential targets of GLP-1 in the treatment of NASH. (Bifari, 2018)

Our Service about NASH

As a first-class and the undisputed world-leader of drug discovery, Creative Biolabs has a "one-stop" drug development service platform, which combines its own advantages to provide customers with a range of technical services about NASH, which include but not limited to:

In addition to NASH-related services, Creative Biolabs also provides drug design (including Hit to Lead, Lead Optimization, IND-Enabling, Target Identification and Validation, Hit identification) and antibody development services (including Phage Display & Antibody Library Services, Antibody Analysis Services, Antibody Engineering Services) based on other diseases. Our service platform is a cost-effective and effective option for you to accelerate the development of drug targets. If you need any services about NASH, please feel free to contact us.

Reference

Bifari, F.; et al. Multiple target tissue effects of GLP-1 analogues on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Pharmacological Research. 2018, 137: 219-229.

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