Unknown

Dataset Information

0

Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents.

ABSTRACT: Fascin is an actin binding and bundling protein that is not expressed in normal epithelial tissues but overexpressed in a variety of invasive epithelial tumors. It has a critical role in cancer cell metastasis by promoting cell migration and invasion. Here we report the crystal structures of fascin in complex with a series of novel and potent inhibitors. Structure-based elaboration of these compounds enabled the development of a series with nanomolar affinities for fascin, good physicochemical properties and the ability to inhibit fascin-mediated bundling of filamentous actin. These compounds provide promising starting points for fascin-targeted anti-metastatic therapies.

SUBMITTER: Francis S 

PROVIDER: S-EPMC6419574 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents.

Francis Stuart S   Croft Daniel D   Schüttelkopf Alexander W AW   Parry Charles C   Pugliese Angelo A   Cameron Ken K   Claydon Sophie S   Drysdale Martin M   Gardner Claire C   Gohlke Andrea A   Goodwin Gillian G   Gray Christopher H CH   Konczal Jennifer J   McDonald Laura L   Mezna Mokdad M   Pannifer Andrew A   Paul Nikki R NR   Machesky Laura L   McKinnon Heather H   Bower Justin J  

Bioorganic & medicinal chemistry letters 20190130 8

Fascin is an actin binding and bundling protein that is not expressed in normal epithelial tissues but overexpressed in a variety of invasive epithelial tumors. It has a critical role in cancer cell metastasis by promoting cell migration and invasion. Here we report the crystal structures of fascin in complex with a series of novel and potent inhibitors. Structure-based elaboration of these compounds enabled the development of a series with nanomolar affinities for fascin, good physicochemical p  ...[more]

Similar Datasets

Unknown Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5-a]pyridine-3-carboxamides as Novel Antitubercular Agents.
| S-EPMC4499832 | biostudies-other
Unknown Design and synthesis of novel pyrazolo[4,3-<i>d</i>]pyrimidines as potential therapeutic agents for acute lung injury.
| S-EPMC6534230 | biostudies-literature
Unknown Tert-butyl 3-oxo-2,3,4,5,6,7-hexa-hydro-1H-pyrazolo[4,3-c]pyridine-5-carboxyl-ate.
| S-EPMC2980051 | biostudies-literature
Unknown Design, Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents.
| S-EPMC8271544 | biostudies-literature
Unknown Synthesis, Structural Characterization, and Biological Activity of New Pyrazolo[4,3-e][1,2,4]triazine Acyclonucleosides.
| S-EPMC6982861 | biostudies-literature
Unknown tert-Butyl 3-amino-2-methyl-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxyl-ate.
| S-EPMC2979268 | biostudies-literature
Unknown A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation.
| S-EPMC7582516 | biostudies-literature
Unknown 1,4-Dimethyl-2-phenyl-6,7-dihydro-1H-pyrazolo-[4,3-b]pyridine-3,5(2H,4H)-dione.
| S-EPMC3201526 | biostudies-other
Unknown 1H-Pyrazolo[4,3-g]benzothia-zol-7-amine.
| S-EPMC2977731 | biostudies-literature
Unknown 5-(4-Chloro-phen-yl)-1-methyl-3-phenyl-3,6,8,9-tetra-hydro-pyrazolo-[3,4-b]thio-pyrano[4,3-d]pyridine.
| S-EPMC3200927 | biostudies-literature