Biguanide Engine
Fibrosis: A Proposed New MOA for Resolution via AMPK Activation
In fibrosis, it is proposed that the loss of AMPK activity promotes persistent myofibroblast activation by deficient autophagy, Extra-cellular Material (ECM) accumulation, mitochondrial dysfunction and acquired apoptosis resistance.
Biguanides are strong AMPK activators and could be effective in treating fibrosis. In the fibrosis model, AMPK activation stimulates autophagy and facilitates ECM turnover, while inducing mitochondrial biogenesis, thus restoring sensitivity to apoptosis and promoting fibrosis resolution.
Unlocking Biguanide Engine Value
ImmunoMet is a cellular metabolism company and is targeting metabolic pathways to address diseases across multiple therapeutic areas. ImmunoMet owns a 1000 molecule biguanide library which forms an engine to develop these novel drugs.
Targeting Mitochondria
In various disease states, particular cell types exhibit dysfunctional cellular metabolism. In fibrosis, fibroblasts may adapt a hyperactive metabolism during differentiation and function that leads to fibrosis. Immune cells adapt a different metabolic strategy in immune related diseases. In cancer, immune suppressor cells can adapt a mitochondrial, OXPHOS-dependent metabolism that allows the cells to coexist with tumor cells, which deplete glucose through highly active glycolytic metabolism. Immune suppressor cells near the tumor limit the full potential of current immunotherapies. The ImmunoMet biguanide engine can target any cell types that use a mitochondrial OXPHOS during disease progression or maintenance.
