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

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

  • ACS Med Chem Lett. 2020 Mar 25;11(5):832-838. doi: 10.1021/acsmedchemlett.9b00639.
Fabrizio Manetti 1 2,  Barbara Stecca 3,  Roberta Santini 3,  Luisa Maresca 3,  Giuseppe Giannini 4,  Maurizio Taddei 1 2,  Elena Petricci 1
Affiliations

Affiliations

  • 1 Dipartimento di Biotecnologie Chimica e Farmacia, Università di Siena, via Aldo Moro 2, I-53100 Siena, Italy.
  • 2 Lead Discovery Siena, via Fiorentina 1, I-53100 Siena, Italy.
  • 3 Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, I-50139 Firenze, Italy.
  • 4 R&D, Alfasigma SpA, I-00071 Pomezia (Roma), Italy.
PMID: 32435392 DOI: 10.1021/acsmedchemlett.9b00639
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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