NASH Target Development Service for CEACAM1 Activators

Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) blockade is a unifying mechanism linking the immunological and metabolic abnormalities in non-alcoholic steatohepatitis (NASH). Based on extensive experience and professional scientists, Creative Biolabs has built a whole set of small molecule drugs/antibody development platforms to discover new therapies for different diseases, including Drug discovery, Hit identification, Hit to Lead, Target Identification and Validation, Lead Optimization. CEACAM1 activators are effective therapeutic strategies we can provide for NASH treatment.

Introduction of CEACAM1 and Its Activators

CEACAM1 is a transmembrane glycoprotein belonging to CEA family of highly glycosylated cellular adhesion molecules. Mainly expressed on epithelial, endothelial and immune cells, CEACAM1 is a differentiation antigen involved in the maintenance of epithelial polarity that is induced during hepatocyte differentiation and liver regeneration. In addition, CEACAM1 is reported to regulate insulin sensitivity by promoting hepatic insulin clearance, and also controls liver tolerance and mucosal immunity. Mounting epidemiological evidence points to an association between CEACAM1 and multiple cancer types. Therefore, CEACAM1 has become an attractive target for cancer immunotherapy because of its multi-faceted role as a recently appreciated immune checkpoint inhibitor and tumor marker.

Fig.1 Structure of CEACAM1.

CEACAM1 Activators for the Treatment of NASH

NASH, an increasingly recognized new epidemic of non-alcoholic fatty liver disease (NAFLD), is a high-risk factor for the development of cirrhosis and hepatocellular carcinoma. Several promising targets and novel therapies possibly reversing fibrosis have been evaluated, such as CEACAM1 activators, which have become an effective treatment strategy for NASH.

It has been demonstrated that loss of CEACAM1 causes fibrosing steatohepatitis which may advance to NASH. Liver-specific inactivation or global null mutation of Ceacam1 gene, as well as its defective phosphorylation, impair the rate of receptor-mediated insulin endocytosis and degradation in the hepatocyte, subsequently, play a pivotal role in insulin resistance, being an independent predictor for fibrosis in NASH. Remarkably, Ceacam1 mutants also develop spontaneous pericellular fibrosis. Collectively, the loss of hepatic CEACAM1 expression (and its resulting hyperinsulinemia and insulin resistance) contributes to the pathogenesis of NASH. As a complementary conclusion, CEACAM1 activators as a promising treatment strategy may improve the biochemical features of fibrosing steatohepatitis (macrosteatosis, inflammation, apoptosis, necrosis, and chicken-wire fibrosis) that progress to NASH.

Fig.2 Regulation of insulin clearance by CEACAM1-L. (Horst, 2018)

As a biological company dedicated to drug discovery and human health research, Creative Biolabs is dedicated to developing and providing global customers with a diversiform portfolio of targets and therapeutic strategies for NASH. Currently, we can provide comprehensive CEACAM1 activators and other useful targets for NASH treatment. In addition, we can offer customized design services to meet every specific demand. Our NASH services include but not limited to:

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

Reference

Horst, A.; et al. CEACAM1 in Liver Injury, Metabolic and Immune Regulation. International journal of molecular sciences. 2018, 19(10): 3110.

For Research Use Only.