Home >> Current Pharmaceutical Design, Volume 6, Number 18

Fibroblast Growth Factors and Their Inhibitors

Authors: Manetti, F.; Corelli, F.; Botta, M.

Source: Current Pharmaceutical Design, Volume 6, Number 18, 1 December 2000 , pp. 1897-1924(28)

Publisher: Bentham Science Publishers

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Abstract:

Fibroblast growth factors (FGFs) are members of a family of polypeptides synthesized by a variety of cell types during the processes of embryonic development and in adult tissues. FGFs have been detected in normal and malignant cells and show a biological profile that includes mitogenic and angiogenic activity with a consequent crucial role in cell differentiation and development. To activate signal transduction pathways, FGFs use a dual receptor system based on tyrosine kinases and heparan sulfate (HS) proteoglycans. Based on these considerations, a variety of inhibitors able to block the interactions between FGFs and their receptors have been designed and investigated for their biological properties related to antiangiogenesis and antitumor activity. In this paper, in addition to an extensive description of the FGF family members, we report several compounds acting as FGF inhibitors by direct interaction with the growth factors. Suramin and other diverse polyanionic polysulfated and polysulfonated compounds are described, with a particular focus on suradistas. For this class of molecules, by means of molecular modeling procedures, a binding model to FGF-2 has been proposed and the structure-activity relationships of suradistas have been analyzed on the basis of the computational model described.
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  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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