Investigation into molecular mechanism of CRV431, a cyclophilin inhibitor, for anti-fibrotic and anti-oncogenic potential in various animal models
Various liver disorders such as fatty liver, liver fibrosis, liver failure and liver cancer, are major healthcare burden and associated with high rate of mortality. Once fatty liver or fibrosis progress to cirrhosis or liver failure, its treatment is challenging due to lack of an effective treatment. Currently available treatment for liver cancer is few anticancer drugs or surgical ablation with liver transplantation. However, available pharmacological interventions have not succeeded fully. In the liver fibrosis events, liver cells start generating extra cellular proteins which interfere with the liver functions as well as activates inflammation in the liver microenvironment. This inflammatory cascade increase liver damage leading to progression of liver cancer. Cyclophilins are known to have role in the progression of various diseases including fatty liver and liver fibrosis. They have central in the metabolic cascade through regulation of mitochondrial, a powerhouse of the cell. Specific inhibitor of cyclophilin, CRV431, has been observed to block the progression of liver fibrosis and liver cancer. CRV431 showed reduced production of extracellular proteins and there by could be useful to diminish the liver fibrosis and associated liver failure and cancer. In this experiment, we will perform various experiments on animals and cells to confirm the therapeutic potential of CRV431.