State of the art of Smo antagonists for cancer therapy: Advances in the target receptor and new ligand structures

Christian Espinosa-Bustos, Jaime Mella, Jorge Soto-Delgado, Cristian O. Salas

Research output: Contribution to journalReview articlepeer-review

18 Citations (Scopus)

Abstract

Since the Hedgehog signaling pathway has been associated with cancer, it has emerged as a therapeutic target for cancer therapy. The main target among the key Hedgehog proteins is the GPCR-like Smo receptor. Therefore, some Smo antagonists that have entered clinical trials, including the US FDA-approved drugs vismodegib and sonidegib, to treat basal cell carcinoma and medulloblastoma. However, early resistance of these drugs has spawned the need to understand the molecular bases of this phenomena. We therefore reviewed details about Smo receptor structures and the best Smo antagonist chemical structures. In addition, we discussed strategies that should be considered to develop new, safer generations of Smo antagonists that avoid current clinical limitations.

Original languageEnglish
Pages (from-to)617-638
Number of pages22
JournalFuture Medicinal Chemistry
Volume11
Issue number6
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

  • anticancer compounds
  • cancer therapy
  • Hedgehog signaling pathway
  • Smo antagonists
  • Smoothened receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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