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

Urmila Jagtap | Zendy; S. Basu | Zendy; Lavanya Lokhande | Zendy; Nikhil Bharti | Zendy; Chetana Sachidanandan | Zendy

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

Author(s) -

Urmila Jagtap,

S. Basu,

Lavanya Lokhande,

Nikhil Bharti,

Chetana Sachidanandan

Publication year - 2022

Publication title -

chemical research in toxicology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.031

H-Index - 156

eISSN - 1520-5010

pISSN - 0893-228X

DOI - 10.1021/acs.chemrestox.2c00100

Subject(s) - liver injury , zebrafish , hepatocyte , acetaminophen , drug , pharmacology , liver damage , small molecule , biology , chemistry , medicine , biochemistry , in vitro , gene

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.

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