Bone-seeking matrix metalloproteinase inhibitors for the treatment of skeletal malignancy

Antonio Laghezza; Luca Piemontese; Leonardo Brunetti; Alessia Caradonna; Mariangela Agamennone; Antonella Di Pizio; Giorgio Pochetti; Roberta Montanari; Davide Capelli; Marilena Tauro; Fulvio Loiodice; Paolo Tortorella

doi:10.3390/ph13060113

Bone-seeking matrix metalloproteinase inhibitors for the treatment of skeletal malignancy

Antonio Laghezza, Luca Piemontese, Leonardo Brunetti, Alessia Caradonna, Mariangela Agamennone, Antonella Di Pizio, Giorgio Pochetti, Roberta Montanari, Davide Capelli, Marilena Tauro, Fulvio Loiodice, Paolo Tortorella

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English
Article number	113
Journal	Pharmaceuticals
Volume	13
Issue number	6
DOIs	https://doi.org/10.3390/ph13060113
State	Published - 2020
Externally published	Yes

Keywords

Antitumor agent
Bisphosphonates
Bone targeting
Matrix metalloproteinase inhibitors
Skeletal malignancies

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ph13060113

Cite this

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title = "Bone-seeking matrix metalloproteinase inhibitors for the treatment of skeletal malignancy",

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.",

keywords = "Antitumor agent, Bisphosphonates, Bone targeting, Matrix metalloproteinase inhibitors, Skeletal malignancies",

author = "Antonio Laghezza and Luca Piemontese and Leonardo Brunetti and Alessia Caradonna and Mariangela Agamennone and {Di Pizio}, Antonella and Giorgio Pochetti and Roberta Montanari and Davide Capelli and Marilena Tauro and Fulvio Loiodice and Paolo Tortorella",

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year = "2020",

doi = "10.3390/ph13060113",

language = "English",

volume = "13",

journal = "Pharmaceuticals",

issn = "1424-8247",

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TY - JOUR

T1 - Bone-seeking matrix metalloproteinase inhibitors for the treatment of skeletal malignancy

AU - Laghezza, Antonio

AU - Piemontese, Luca

AU - Brunetti, Leonardo

AU - Caradonna, Alessia

AU - Agamennone, Mariangela

AU - Di Pizio, Antonella

AU - Pochetti, Giorgio

AU - Montanari, Roberta

AU - Capelli, Davide

AU - Tauro, Marilena

AU - Loiodice, Fulvio

AU - Tortorella, Paolo

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Antitumor agent

KW - Bisphosphonates

KW - Bone targeting

KW - Matrix metalloproteinase inhibitors

KW - Skeletal malignancies

UR - http://www.scopus.com/inward/record.url?scp=85086014386&partnerID=8YFLogxK

U2 - 10.3390/ph13060113

DO - 10.3390/ph13060113

M3 - Article

AN - SCOPUS:85086014386

SN - 1424-8247

VL - 13

JO - Pharmaceuticals

JF - Pharmaceuticals

IS - 6

M1 - 113

ER -

Bone-seeking matrix metalloproteinase inhibitors for the treatment of skeletal malignancy

Abstract

Keywords

UN SDGs

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