Eurofins Discovery offers in-depth MASH drug discovery services, from target- and translational-based portfolios to in vivo efficacy studies, using advanced cellular and animal models closely resembling clinical conditions.
Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is the severe form of MASLD (metabolic dysfunction-associated steatotic liver disease)*, which affects almost 25% of the world population with high overlap of type-2 diabetes and obesity. Due to its complex pathophysiology, novel and diverse therapeutic strategies have been explored, with more than 40 emerging targets currently under clinically investigation. Of these, THRβ, FXR, FGFR, PPAR as well as GLP1R combination therapies are the most intensively studied. With the first MASH drug targeting THRβ being FDA-approved in March 2024, the next wave of new MASH therapies is rising followed by more promising mechanisms against this difficult-to-treat liver disease.
Our MASH LeadHunter® Panel (PP318) contains the most clinically relevant targets (e.g., THRβ, FXR, PPAR) which are highly engaged in glucose, lipid, and bile acid metabolisms, as well as inflammatory, apoptotic, and fibrotic effects. This target-based panel enables a comprehensive understanding of the mechanism of action (MOA) from steatosis and hepatitis to fibrosis. Next, the therapeutic efficacy can be seamlessly evaluated with the translational TGFβ-induced liver fibrosis cell model (Figure 1A), and BioMAP® MyoF fibrosis model. These platforms are specifically designed for screening anti-fibrotic agents, providing valuable insights for promising candidates and advancing them to the next stage of drug discovery.
Our partner lab, Pharmacology Discovery Services (PDS), also offers three in vivo MASH models, including the unique CDAHFD-induced humanized liver chimeric mice (HLCM) model (Figure 1B) where the liver is engrafted with up to 95% of human hepatocytes, featuring a human-like liver environment. The MASH model in HLCM is more clinically relevant and would be used more in the late preclinical. Our integrated approaches enable rapid identification of promising drugs and mechanisms for MASH drug discovery and development.
*To improve disease awareness and prevent potential stigmatization, experts across 56 countries reached a consensus in 2023 on a new nomenclature of fatty liver disease. NAFLD was renamed to MASLD (metabolic dysfunction-associated steatotic liver disease), while the new NASH nomenclature is now MASH (metabolic dysfunction-associated steatohepatitis). (Rinella, Mary E et al. “A multisociety Delphi consensus statement on new fatty liver disease nomenclature.” Hepatology (Baltimore, Md.) vol. 78,6 (2023): 1966-1986.)
Figure 1: Demonstrative data of the TGFβ-induced liver fibrosis cell model (A.) and the CDAHFD-induced HLCM model (B.). A. TGFβ successfully induced human hepatic stellate cell line LX-2 activation. Reported TGFβ inhibitors significantly suppressed COL1A1 expression in a dose-dependent manner. B. Liver steatosis, hepatocellular ballooning, and fibrosis were successfully induced after CDAHFD feeding in HLCM while applied clinical candidate obeticholic acid (OCA) significantly reduced total NAS + fibrosis score at 6 and 12 weeks.
View/Order in vitro MASH panel and translational models:
MASH LeadHunter Panel
Liver fibrosis collagen type I Human Functional Antagonist Assay
BioMAP Fibrosis Panel
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Diabetes Drug Discovery
The number of people suffering from diabetes will be 640 million by 2030 and reach 780 million by 2045. Amongst all diabetic patients, Type 2 diabetes (T2D) is the predominant form. The progression of T2D is due to a loss of adequate insulin secretion and the inability of insulin-sensitive tissues to respond to insulin (insulin resistance). Combination therapy with drugs of different mechanisms is often applied to better maintain blood glucose levels for T2D patients. However, there is an unmet need for a better treatment due to inadequate efficacy accompanied by undesirable side effects. Similar to MASH drug discovery, a multi-target approach (e.g., GLP1R/GIPR/GCGR, SGLT1/2, and GCK/GPR40/GPR119/11 b-HSD1, etc.) has served as a promising therapeutic strategy for T2D.
Eurofins Discovery offers two specialized diabetes panels – Insulin Release LeadHunter Panel (PP277) and Insulin Sensitivity LeadHunter Panel (PP278), with a total of 17 therapeutic targets highly involved in insulin secretion and resistance pathways, to assist MOA understanding and multi-target effects for your potential compounds.
Following in vitro assay characterization, drug efficacy could be further evaluated via in vivo diabetes models. Our partner lab, PDS, provides several in vivo diabetic rodent models for efficacy assessment.
Figure 1: Demonstrative data of the Insulin Release Panel (A.) and the Insulin Sensitivity Panel (B.). A. Reported clinical candidates, PF-04991532 and dorzagliatin, were validated through the enzymatic GCK activation assay. B. Reported 11β-HSD1 inhibitors, PF-915275 and BVT-2733, were validated by the enzymatic 11β-HSD1 inhibition assay.
View/Order in vitro diabetes panels:
Insulin Release LeadHunter Panel
Insulin Sensitivity LeadHunter Panel
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Features and Benefits
- High clinical relevance: More than 80% of listed therapeutic targets are under clinical development, and a humanized liver chimeric mouse model is used as an in vivo MASH model
- In-depth MOA evaluation: Combining target- and translational-based assays to comprehensively characterize molecular mechanisms and multi-target effects
- One-stop solution: Seamlessly follow up to in vivo animal disease model evaluation
- Flexibility: Assays in these panels can be ordered individually or as a full panel service
- Tailor-made: Customization of panels to clients’ needs
