Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 20, Issue 21, Pages 6465-6481Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2012.08.026
Keywords
Hedgehog; SAG; VEGF
Funding
- TRM-Translational Centre of Regenerative Medicine Leipzig
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Here, we describe the synthesis, SAR studies as well as biological investigations of the known Hedgehog signaling agonist SAG and a small library of its analogues. The SAG and its derivatives were analyzed for their potency to activate the expression of the Hh target gene Gli1 in a reporter gene assay. By analyzing SAR important molecular descriptors for Gill activation have been identified. SAG as well as compound 10c proven to be potent activators of VEGF expression in cultivated dermal fibroblasts. Importantly and in contrast to SAG, derivative 10c displayed no toxicity in concentrations up to 250 mu m. (C) 2012 Elsevier Ltd. All rights reserved.
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