Pharmacophore modeling and virtual screening for the discovery of new transforming growth factor-beta type I receptor (ALK5) inhibitors.

Article Details

Citation

Copy to clipboard

Ren JX, Li LL, Zou J, Yang L, Yang JL, Yang SY

Pharmacophore modeling and virtual screening for the discovery of new transforming growth factor-beta type I receptor (ALK5) inhibitors.

Eur J Med Chem. 2009 Nov;44(11):4259-65. doi: 10.1016/j.ejmech.2009.07.008. Epub 2009 Jul 16.

PubMed ID

19640613 [ View in PubMed

]

Abstract

Inhibitors of transforming growth factor-beta Type I Receptor (ALK5) have been thought as potential drugs for the treatment of fibrosis and cancer and a considerable number of ALK5 inhibitors have been reported recently. In order to clarify the essential structure-activity relationship for the known ALK5 inhibitors as well as identify new lead compounds against ALK5, 3D pharmacophore models have been established based on the known ALK5 inhibitors. The best pharmacophore model, Hypo1, was used as a 3D search query to perform a virtual screening. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five and docking studies to refine the retrieved hits. Finally a total of 100 compounds were obtained and some of them were selected for further in vitro and in vivo assay studies.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
3-(4-Fluorophenyl)-2-(6-Methylpyridin-2-Yl)-5,6-Dihydro-4h-Pyrrolo[1,2-B]Pyrazole	TGF-beta receptor type-1	IC 50 (nM)	1320	N/A	N/A	Details
4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinoline	TGF-beta receptor type-1	IC 50 (nM)	51	N/A	N/A	Details