Potent small molecule Hedgehog agonists induce VEGF expression in vitro

被引：21

作者：

Seifert, Katrin ^{[1
]}

Buettner, Anita ^{[1
]}

Rigol, Stephan ^{[1
]}

Eilert, Nicole ^{[1
]}

Wandel, Eike ^{[2
]}

Giannis, Athanassios ^{[1
]}

机构：

[1] Univ Leipzig, Inst Organ Chem, Fak Chem & Mineral, D-04103 Leipzig, Germany

[2] TRM Leipzig, Res Labs, Dept Surg, D-04103 Leipzig, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 21期

关键词：

Hedgehog; SAG; VEGF; SONIC HEDGEHOG; HAIR FOLLICLE; ENDOTHELIAL-CELLS; GENE-THERAPY; STEM-CELLS; IDENTIFICATION; MORPHOGENESIS; INHIBITORS; PROTEINS; PATHWAY;

D O I：

10.1016/j.bmc.2012.08.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：6465 / 6481

页数：17

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