Optimization of the TeraTox Assay for Preclinical Teratogenicity Assessment.

ABSTRACT: Current animal-free methods to assess teratogenicity of drugs under development still deliver high numbers of false negatives. To improve the sensitivity of human teratogenicity prediction, we characterized the TeraTox test, a newly developed multilineage differentiation assay using 3D human-induced pluripotent stem cells. TeraTox produces primary output concentration-dependent cytotoxicity and altered gene expression induced by each test compound. These data are fed into an interpretable machine-learning model to perform prediction, which relates to the concentration-dependent human teratogenicity potential of drug candidates. We applied TeraTox to profile 33 approved pharmaceuticals and 12 proprietary drug candidates with known in vivo data. Comparing TeraTox predictions with known human

SUBMITTER: Jaklin M 

PROVIDER: S-EPMC9237991 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature