BML-257, a Small Molecule that Protects against Drug-Induced Liver Injury in Zebrafish.

Urmila Jagtap, Sandeep Basu, Lavanya Lokhande, Nikhil Bharti, Chetana Sachidanandan

Chemical research in toxicology 2022 Aug 15

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The use of many essential drugs is restricted due to their deleterious effects on the liver. Molecules that can prevent or protect the liver from drug-induced liver injury (DILI) would be invaluable in such situations. We used a transgenic line in zebrafish with a hepatocyte-specific expression of bacterial nitroreductase to cause temporally controlled liver damage. A whole organism-based chemical screen using the transgenic line identified BML-257, a potent small molecule AKT inhibitor, that protected the liver against metronidazole-induced liver injury. BML-257 also showed potent prophylactic and pro-regenerative activity in this liver damage model. BML-257 was tested in two independent toxicological models of liver injury caused by acetaminophen and isoniazid and was found to be protective against damage. This suggests that BML-257 has the potential to protect against multiple kinds of DILI.

Citation

Urmila Jagtap, Sandeep Basu, Lavanya Lokhande, Nikhil Bharti, Chetana Sachidanandan. BML-257, a Small Molecule that Protects against Drug-Induced Liver Injury in Zebrafish. Chemical research in toxicology. 2022 Aug 15;35(8):1393-1399