BioCentury
ARTICLE | Distillery Therapeutics

Hepatic

August 23, 2018 3:49 PM UTC

Mouse studies suggest inhibiting TGFBR1 could help treat liver disease and DILI. In mouse models of chemical-induced chronic and acute liver injury, hepatocyte-specific knockout of TGFBR1 or a tool compound TGFBR1 inhibitor decreased hepatocyte senescence and increased hepatocyte proliferation compared with normal TGFBR1 expression or vehicle, respectively. In a mouse model of acetaminophen-induced acute liver injury, administration 12 hours after liver injury of the TGFBR1 inhibitor or a second tool compound TGFBR1 inhibitor decreased serum bilirubin and hepatocyte senescence in the perinecrotic area of the liver compared with vehicle, and administration of the first TGFBR1 inhibitor at the time of liver injury increased survival. Next steps include testing undisclosed TGFBR1 inhibitors in patients with acetaminophen overdose-associated acute liver injury.

Eli Lilly and Co. has galunisertib (LY2157299), a TGFBR1 inhibitor, in Phase II testing for brain cancer and liver cancer and Phase I/II testing for pancreatic cancer...