NASH Target Development Service for Carnitine Palmitoyltransferase-1 (CPT-1) Activators

Drug discovery for novel NASH therapies is extensive and there are promising approaches in all stages of clinical development. Creative Biolabs has extensive experience and a high-end platform and state-of-the-art technology in drug discovery. We can offer the services of CPT-1 activators development for the treatment of NASH through alleviating hepatic lipid deposition.

Introduction of Carnitine Palmitoyltransferase-1 (CPT-1) Activators

Carnitine palmitoyl transferase-1 (CPT-1) is one of the key rate-limiting enzymes regulating fatty acid metabolism in the mitochondrial membrane and the mitochondrial gateway for fatty acid entry into the matrix. CPT-1 is responsible for β-oxidation of free fatty acids (FFA) in mitochondria, and also determines the cytosolic concentration of long-chain acyl-CoA esters. It catalyzes the conversion of long-chain acyl-CoA to acylcarnitine, which enters the mitochondrial matrix and undergoes β-oxidation. The decrease of CPT-1 activity severely affects mitochondrial fatty acid oxidation (FAO) and induces the accumulation of FFA and triglycerides, lower production of ketone bodies and reduces ATP synthesis. The accumulation of FFA may play a major role in the pathophysiology of some diseases. In addition, it can cause an impairment of energy output in the liver and in extra-hepatic tissues due to the lower ketone body production. CPT-1 activators can significantly increase the activity of CPT-1 and thereby enhance the β-oxidation of fatty acids to reduce the accumulation of lipids, which provides a new strategy for the treatment of some metabolic disorders.

Fig.1 Metabolic consequences of inhibition of mitochondrial fatty acid β-oxidation. (Begriche, 2011)

Carnitine Palmitoyltransferase-1 (CPT-1) Activators for NASH Treatment

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease that has been linked to mitochondrial dysfunction and more specifically fatty acid β-oxidative damage. CPT-1 is an essential enzyme responsible for β-oxidation of FFA in mitochondria, from lipotoxicity, thus alleviating hepatic lipid deposition. As CPT-1 activity increases, a large amount of FFA could be transported into the mitochondria where it is subject to β-oxidation. CPT-1 activators, such as hepatic stimulator substance (HSS), increase CPT-1 activity and finally enhance FFA transport to the mitochondria where it is degraded, thereby facilitating the clearance of excessive hepatic lipids during NASH formation and improving NASH. In conclusion, CPT-1 activators protect the liver from NASH injury through the regulation of the mitochondrial lipid metabolism via enhancement of CPT-1 activity and subsequent β-oxidation of fatty acids in mitochondria.

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. In addition to target discovery, we also provide antibody development services (including Phage Display & Antibody Library Services, Antibody Analysis Services, Antibody Engineering Services) to better treat NASH with more options. 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

1. Begriche, K.; et al. Drug-induced toxicity on mitochondria and lipid metabolism: Mechanistic diversity and deleterious consequences for the liver. Journal of Hepatology. 2011, 54(4): 773-794.