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Chem Soc Rev. 2011 Aug;40(8):4318-31. doi: 10.1039/c1cs15019g. Epub 2011 Apr 19.

Chemical 'Jekyll and Hyde's: small-molecule inhibitors of developmental signaling pathways.

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1
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

Small molecules that perturb developmental signaling pathways can have devastating effects on embryonic patterning, as evidenced by the chemically induced onset of cyclopic lambs and children with severely shortened limbs during the 1950s. Recent studies, however, have revealed critical roles for these pathways in human disorders and diseases, spurring the re-examination of these compounds as new targeted therapies. In this tutorial review, we describe four case studies of teratogenic compounds, including inhibitors of the Hedgehog (Hh), Wnt, and bone morphogenetic protein (BMP) pathways. We discuss how these teratogens were discovered, their mechanisms of action, their utility as molecular probes, and their potential as therapeutic agents. We also consider current challenges in the field and possible directions for future research.

PMID:
21505654
PMCID:
PMC3137710
DOI:
10.1039/c1cs15019g
[Indexed for MEDLINE]
Free PMC Article
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