Bone-Seeking Matrix Metalloproteinase Inhibitors for the Treatment of Skeletal Malignancy

Author:

Laghezza AntonioORCID,Piemontese LucaORCID,Brunetti LeonardoORCID,Caradonna Alessia,Agamennone MariangelaORCID,Di Pizio AntonellaORCID,Pochetti GiorgioORCID,Montanari Roberta,Capelli DavideORCID,Tauro MarilenaORCID,Loiodice Fulvio,Tortorella PaoloORCID

Abstract

Matrix metalloproteinases (MMPs) are a family of enzymes involved at different stages of cancer progression and metastasis. We previously identified a novel class of bisphosphonic inhibitors, selective for MMPs crucial for bone remodeling, such as MMP-2. Due to the increasing relevance of specific MMPs at various stages of tumor malignancy, we focused on improving potency towards certain isoforms. Here, we tackled MMP-9 because of its confirmed role in tumor invasion, metastasis, angiogenesis, and immuno-response, making it an ideal target for cancer therapy. Using a computational analysis, we designed and characterized potent MMP-2/MMP-9 inhibitors. This is a promising approach to develop and clinically translate inhibitors that could be used in combination with standard care therapy for the treatment of skeletal malignancies.

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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