Mechanisms to inhibit matrix metalloproteinase activity: Where are we in the development of clinically relevant inhibitors?

Christian A. Corbitt, Jing Lin, Merry L. Lindsey

Research output: Contribution to journalReview article

29 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) are involved in numerous pathophysiological processes, including cancer and cardiovascular disease. MMPs proteolyze multiple targets, including extracellular matrix, cytokines, and growth factors. Due to a high clinical relevance, MMPs have long been a target for pharmaceutical intervention. Although numerous drug therapies to inhibit MMPs have been explored, only one agent (doxycycline hyclate) is currently approved for clinical use. Multiple reasons potentially explain the lack of success in developing MMP inhibitors, including issues with selectivity and specificity and the presence of multiple substrates with conflicting functions. Major recent advances in the MMP field include an increased understanding of MMP biology, the improved establishment of parameters to adequately evaluate efficacy, and methods to enhance inhibitor design. This review will explore the latest research and patents targeted at MMP inhibition, and will focus on both direct and indirect mechanisms to block MMPs.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalRecent Patents on Anti-Cancer Drug Discovery
Volume2
Issue number2
DOIs
StatePublished - Jun 1 2007

Fingerprint

Matrix Metalloproteinases
Matrix Metalloproteinase Inhibitors
Patents
Doxycycline
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Cardiovascular Diseases
Cytokines
Drug Therapy
Research
Pharmaceutical Preparations
Neoplasms

Keywords

  • Cancer
  • Hydroxamate
  • MMP inhibitors
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Cancer Research
  • Pharmacology (medical)

Cite this

Mechanisms to inhibit matrix metalloproteinase activity : Where are we in the development of clinically relevant inhibitors? / Corbitt, Christian A.; Lin, Jing; Lindsey, Merry L.

In: Recent Patents on Anti-Cancer Drug Discovery, Vol. 2, No. 2, 01.06.2007, p. 135-142.

Research output: Contribution to journalReview article

@article{3fb2bd6919bc42b9bd889bc00e2f0dc0,
title = "Mechanisms to inhibit matrix metalloproteinase activity: Where are we in the development of clinically relevant inhibitors?",
abstract = "Matrix metalloproteinases (MMPs) are involved in numerous pathophysiological processes, including cancer and cardiovascular disease. MMPs proteolyze multiple targets, including extracellular matrix, cytokines, and growth factors. Due to a high clinical relevance, MMPs have long been a target for pharmaceutical intervention. Although numerous drug therapies to inhibit MMPs have been explored, only one agent (doxycycline hyclate) is currently approved for clinical use. Multiple reasons potentially explain the lack of success in developing MMP inhibitors, including issues with selectivity and specificity and the presence of multiple substrates with conflicting functions. Major recent advances in the MMP field include an increased understanding of MMP biology, the improved establishment of parameters to adequately evaluate efficacy, and methods to enhance inhibitor design. This review will explore the latest research and patents targeted at MMP inhibition, and will focus on both direct and indirect mechanisms to block MMPs.",
keywords = "Cancer, Hydroxamate, MMP inhibitors, Matrix metalloproteinases",
author = "Corbitt, {Christian A.} and Jing Lin and Lindsey, {Merry L.}",
year = "2007",
month = "6",
day = "1",
doi = "10.2174/157489207780832423",
language = "English (US)",
volume = "2",
pages = "135--142",
journal = "Recent Patents on Anti-Cancer Drug Discovery",
issn = "1574-8928",
publisher = "Bentham Science Publishers B.V.",
number = "2",

}

TY - JOUR

T1 - Mechanisms to inhibit matrix metalloproteinase activity

T2 - Where are we in the development of clinically relevant inhibitors?

AU - Corbitt, Christian A.

AU - Lin, Jing

AU - Lindsey, Merry L.

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Matrix metalloproteinases (MMPs) are involved in numerous pathophysiological processes, including cancer and cardiovascular disease. MMPs proteolyze multiple targets, including extracellular matrix, cytokines, and growth factors. Due to a high clinical relevance, MMPs have long been a target for pharmaceutical intervention. Although numerous drug therapies to inhibit MMPs have been explored, only one agent (doxycycline hyclate) is currently approved for clinical use. Multiple reasons potentially explain the lack of success in developing MMP inhibitors, including issues with selectivity and specificity and the presence of multiple substrates with conflicting functions. Major recent advances in the MMP field include an increased understanding of MMP biology, the improved establishment of parameters to adequately evaluate efficacy, and methods to enhance inhibitor design. This review will explore the latest research and patents targeted at MMP inhibition, and will focus on both direct and indirect mechanisms to block MMPs.

AB - Matrix metalloproteinases (MMPs) are involved in numerous pathophysiological processes, including cancer and cardiovascular disease. MMPs proteolyze multiple targets, including extracellular matrix, cytokines, and growth factors. Due to a high clinical relevance, MMPs have long been a target for pharmaceutical intervention. Although numerous drug therapies to inhibit MMPs have been explored, only one agent (doxycycline hyclate) is currently approved for clinical use. Multiple reasons potentially explain the lack of success in developing MMP inhibitors, including issues with selectivity and specificity and the presence of multiple substrates with conflicting functions. Major recent advances in the MMP field include an increased understanding of MMP biology, the improved establishment of parameters to adequately evaluate efficacy, and methods to enhance inhibitor design. This review will explore the latest research and patents targeted at MMP inhibition, and will focus on both direct and indirect mechanisms to block MMPs.

KW - Cancer

KW - Hydroxamate

KW - MMP inhibitors

KW - Matrix metalloproteinases

UR - http://www.scopus.com/inward/record.url?scp=34250776006&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250776006&partnerID=8YFLogxK

U2 - 10.2174/157489207780832423

DO - 10.2174/157489207780832423

M3 - Review article

C2 - 18221058

AN - SCOPUS:34250776006

VL - 2

SP - 135

EP - 142

JO - Recent Patents on Anti-Cancer Drug Discovery

JF - Recent Patents on Anti-Cancer Drug Discovery

SN - 1574-8928

IS - 2

ER -