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We are analyzing https://www.nature.com/articles/nrc1821.

Title:
Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy | Nature Reviews Cancer
Description:
Clinical trial results with matrix metalloproteinase (MMP) inhibitors have been poor. So, which MMPs are validated drug targets with a crucial role in disease pathogenesis and which MMPs are actually proteins that have unacceptable deleterious effects when inhibited (anti-targets)? The matrix metalloproteinases (MMPs) mediate homeostasis of the extracellular environment. They have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs. However, there are many criteria to consider in validating MMPs as drug targets and for the development of MMP inhibitors. The inhibition of some MMPs could have pro-tumorigenic effects (making them anti-targets), counterbalancing the benefits of target inhibition. These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?
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30 years and 10 months (reg. 1994-08-11).

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Education
Health & Fitness
Science

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Custom-built

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🌆 Monumental Traffic: 20M - 50M visitors per month

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$536,300 per month
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google, scholar, pubmed, cas, cancer, nature, matrix, metalloproteinase, breast, cell, inhibitors, biol, central, res, metalloproteinases, mmp, rev, human, chem, expression, access, cells, mice, article, drug, metastasis, research, therapy, tumor, med, british, columbia, content, target, collagen, matrisian, cookies, development, inhibition, science, protease, progression, privacy, targets, christopher, mmps, clinical, validation, open, discovery,

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permissions reprints nature portfolio privacy policy advertising mcp-1-tnfα cross-regulatory pathway cancer cell–adipocyte interaction/crosstalk discovery tools isotope-coded affinity tags author information authors double-blind placebo-controlled antisense rna-induced reduction blood research mmp-inhibitor-drug development biomedical research modify n-timp2 specificity isotope dilution-mass spectrometry author correspondence monocyte chemoattractant protein-3 nature cell biol national cancer institute social media ebsco media breast cancer development blood–brain barrier disruption cxcl12–cxcr4 chemotactic pathway leukolysin/mt6-mmp/mmp-25 gelatinase a-deficient mice personal data reciprocal tumor–microenvironment interactions mechanism-based gelatinase inhibitor springerlink instant access data protection permissions nature rev mass spectrometry-based proteomics nature neurosci structure-based drug design nature genet nature biotechnol nature med growth factor res canadian cancer association diet-induced obesity distinct collagen binding metalloproteinase substrate specificity metastatic potential correlates ben-baruch nature 284 nature 436 nature 390

Questions {❓}

What are the major challenges in MMP target validation and MMP-inhibitor-drug development?

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