Virtual drug screen reveals context-dependent inhibition of cardiomyocyte hypertrophy.

ABSTRACT:

Background and purpose

Pathological cardiomyocyte hypertrophy is a response to cardiac stress that typically leads to heart failure. Despite being a primary contributor to pathological cardiac remodelling, the therapeutic space that targets hypertrophy is limited. Here, we apply a network model to virtually screen for FDA-approved drugs that induce or suppress cardiomyocyte hypertrophy.

Experimental approach

A logic-based differential equation model of cardiomyocyte signalling was used to predict drugs that modulate hypertrophy. These predictions were validated against curated experiments from the prior literature. The actions of midostaurin were validated in new experiments using TGFβ- and noradrenaline (NE)-induced hypertrophy in neonatal rat cardiomyocytes.

Key results

SUBMITTER: Eggertsen TG 

PROVIDER: S-EPMC10592153 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature