HepaRegeniX - A First-in-class Therapeutic Target
Details
Since 2017, HepaRegeniX has identified several small molecule inhibitors of MKK4 as part of its targeted drug discovery efforts. These molecules recently produced successful preclinical results in several animal models which led to start of clinical development for HRX-0215 as the first MKK4 inhibitor from the company´s small molecule-based liver regeneration platform. First proof for for pharmacologically induced benefits in non-rodent model in a collaboration with Mayo clinic were presented at AASLD 2020. In December 2020, it was shown, that treatment with selective Mitogen-Activated Protein (MAP) Kinase Kinase 4 (MKK4) inhibitors over a three-month period reduced hepatic steatosis and liver damage in a murine model of nonalcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC). MKK4 inhibition was not only safe and well tolerated but even showed marked growth suppression of NASH-associated hepatocellular carcinoma.
Most, specifically, HepaRegenix was able to demonstrate that MKK4 inhibition causes
- An enhancement of hepatocyte proliferation in mice and pigs
- A general increase of hepatocyte robustness
- A significant reduction of alcohol-induced steatosis, chronic NASH and NASH-HCC
- A reduction of liver lipids without affecting body or liver weight and a prevention of tumor progression
In addition to a possible use in liver regeneration, HepaRegeniX recognizes potential for MKK4 inhibition in a range of other indications, including cancer. In this respect, the company has recently initiated a collaboration with NKI to investigate the use of MKK4 inhibitors for cancer combination therapy.
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