Pharmacophore-Based Virtual Screening for Identification of Negative Modulators of GLI1 as Potential Anticancer Agents.

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.

SUBMITTER: Manetti F 

PROVIDER: S-EPMC7236221 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature