Citation:

Baker, N., J. Pierro, L. Taylor, AND T. Knudsen. Identifying candidate reference chemicals for in vitro testing of the retinoid pathway for predictive developmental toxicity. ALTEX. Society ALTEX Edition, Kuesnacht, Switzerland, 40(2):217-236, (2023). https://doi.org/10.14573/altex.2202231

Impact/Purpose:

The identification of chemical compounds that can be used to probe different aspects of the the all-trans retinoic acid (ATRA) signaling pathway will support OECD Testing and Assessment Series No. 343.  

Description:

Evaluating chemicals for potential in vivo toxicity based on their in vitro bioactivity profile is an important step toward animal-free testing. A compendium of reference chemicals and data describing their bioactivity on specific molecular targets, cellular pathways, and biological processes is needed to bolster confidence in the predictive value of in vitro hazard detection. Endogenous signaling by all-trans retinoic acid (ATRA) is an important pathway in developmental processes and toxicities. Employing data extraction methods and advanced literature extraction tools, we assembled a set of candidate reference chemicals for activity on ten protein family targets in the retinoid system (serum retinol binding protein, stimulated by retinoic acid 6, cellular retinol binding protein, cellular retinoic acid binding protein, retinoic acid 4-hydroxylase (CYP26), retinol dehydrogenase, retinal dehydrogenase, retinoic acid receptors alpha, beta and gamma) and their downstream cellular consequences. The compendium was culled from Protein Data Bank, ChEMBL, ToxCast/Tox21, and the biomedical literature in PubMed. We also deliver an updated Abstract Sifter tool populated with these reference compounds and complex search terms designed to query the literature for the downstream consequences to support concordance with targeted retinoid pathway disruption.

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