Pharmacophore-Based Virtual Screening for Identification of Negative Modulators of GLI1 as Potential Anticancer
Fabrizio Manetti1,2, Barbara Stecca3, Roberta Santini3
1Dipartimento di Biotecnologie Chimica e Farmacia, Università di Siena, via Aldo Moro 2, I-53100 Siena, Italy.
Abstract:
Starting from known GLI1 inhibitors, a pharmacophore-based virtual screening approach was applied to databases of commercially available compounds with the aim of identifying new GLI1 modulators. As a result, three different chemical scaffolds emerged that were characterized by a significant ability to reduce the transcriptional activity of the endogenous Hedgehog-GLI pathway and GLI1 protein level in murine NIH3T3 cells. They also showed a micromolar antiproliferative activity in human melanoma (A375) and medulloblastoma (DAOY) cell lines, without cytotoxicity in non-neoplastic mammary epithelial cells.
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