During tumor angiogenesis different growth factors, cytokines and other molecules interact closely with each other to facilitate tumor cell invasion and metastatic diffusion. The most intensively studied as molecular targets in anti-angiogenic therapies are vascular endothelial growth factor (VEGF) and related receptors, integrin receptors and matrix metalloproteinases (MMPs). Considering the poor efficacy of cancer angiogenesis monotherapies, we reasoned combining the inhibition of αvβ3 and MMP2 as a multitarget approach to deliver a synergistic blockade of tumor cell migration, invasion and metastasis. Accordingly, we identified a common pharmacophore in the binding cavity of MMP2 and αvβ3, demonstrating such approach with the design, synthesis and bioassays of tyrosine-derived peptidomimetics carrying the necessary functional groups to bind to key pharmacophoric elements of MMP2 and αvβ3 RGD integrin.

Identification of a Common Pharmacophore for Binding to MMP2 and RGD Integrin: Towards a Multitarget Approach to Inhibit Cancer Angiogenesis and Metastasis / Baldini, Lorenzo; Lenci, Elena; Bianchini, Francesca; Trabocchi, Andrea. - In: MOLECULES. - ISSN 1420-3049. - ELETTRONICO. - 27:(2022), pp. 0-0. [10.3390/molecules27041249]

Identification of a Common Pharmacophore for Binding to MMP2 and RGD Integrin: Towards a Multitarget Approach to Inhibit Cancer Angiogenesis and Metastasis

Baldini, Lorenzo;Lenci, Elena;Bianchini, Francesca;Trabocchi, Andrea
2022

Abstract

During tumor angiogenesis different growth factors, cytokines and other molecules interact closely with each other to facilitate tumor cell invasion and metastatic diffusion. The most intensively studied as molecular targets in anti-angiogenic therapies are vascular endothelial growth factor (VEGF) and related receptors, integrin receptors and matrix metalloproteinases (MMPs). Considering the poor efficacy of cancer angiogenesis monotherapies, we reasoned combining the inhibition of αvβ3 and MMP2 as a multitarget approach to deliver a synergistic blockade of tumor cell migration, invasion and metastasis. Accordingly, we identified a common pharmacophore in the binding cavity of MMP2 and αvβ3, demonstrating such approach with the design, synthesis and bioassays of tyrosine-derived peptidomimetics carrying the necessary functional groups to bind to key pharmacophoric elements of MMP2 and αvβ3 RGD integrin.
2022
27
0
0
Baldini, Lorenzo; Lenci, Elena; Bianchini, Francesca; Trabocchi, Andrea
File in questo prodotto:
File Dimensione Formato  
molecules-27-01249.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Creative commons
Dimensione 8.6 MB
Formato Adobe PDF
8.6 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1256659
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 3
social impact