Matrix metalloproteinases (MMP) are calcium- and zinc-dependent proteinases regulating the extracellular matrix and are often divided (e.g. [13]) on functional and structural bases into gelatinases, collagenases, stromyelinases and matrilysins, as well as membrane type-MMP (MT-MMP).

A number of small molecule ‘broad spectrum’ inhibitors of MMP have been described, including marimastat and batimastat.

Tissue inhibitors of metalloproteinase (TIMP) proteins are endogenous inhibitors acting to chelate MMP proteins: TIMP1 (TIMP1, P01033), TIMP2 (TIMP2, P16035), TIMP3 (TIMP3, P35625), TIMP4 (TIMP4, Q99727)

1. Abbenante G, Fairlie DP. (2005) Protease inhibitors in the clinic. Med Chem, 1 (1): 71-104. [PMID:16789888]

2. AstraZeneca. AZD1236. Accessed on 31/10/2014. Modified on 31/10/2014. Open Innovation, http://openinnovation.astrazeneca.com/what-we-offer/compound/azd1236/

3. Chen JM, Nelson FC, Levin JI, Mobilio D, Moy FJ, Nilakantan R, Zask A, Powers R. (2000) Structure-Based Design of a Novel, Potent, and Selective Inhibitor for MMP-13 Utilizing NMR Spectroscopy and Computer-Aided Molecular Design. J Am Chem Soc, 122 (40): 9648-9654. DOI: 10.1021/ja001547g

4. Cobos-Correa A, Stein F, Schultz C. (2012) Target-Activated Prodrugs (TAPs) for the Autoregulated Inhibition of MMP12. ACS Med Chem Lett, 3 (8): 653-7. [PMID:24900526]

5. Czarny B, Stura EA, Devel L, Vera L, Cassar-Lajeunesse E, Beau F, Calderone V, Fragai M, Luchinat C, Dive V. (2013) Molecular determinants of a selective matrix metalloprotease-12 inhibitor: insights from crystallography and thermodynamic studies. J Med Chem, 56 (3): 1149-59. [PMID:23343195]

6. Freeman-Cook KD, Reiter LA, Noe MC, Antipas AS, Danley DE, Datta K, Downs JT, Eisenbeis S, Eskra JD, Garmene DJ et al.. (2007) Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13. Bioorg Med Chem Lett, 17 (23): 6529-34. [PMID:17935984]

7. García RA, Pantazatos DP, Gessner CR, Go KV, Woods Jr VL, Villarreal FJ. (2005) Molecular interactions between matrilysin and the matrix metalloproteinase inhibitor doxycycline investigated by deuterium exchange mass spectrometry. Mol Pharmacol, 67 (4): 1128-36. [PMID:15665254]

8. Moriyama H, Tsukida T, Inoue Y, Yokota K, Yoshino K, Kondo H, Miura N, Nishimura S. (2004) Azasugar-based MMP/ADAM inhibitors as antipsoriatic agents. J Med Chem, 47 (8): 1930-8. [PMID:15055993]

9. MRC. AZD6605 Matrix metallopeptidase 13 (MMP13) inhibitor. Accessed on 28/10/2014. Modified on 28/10/2014. MRC/AstraZeneca: Mechanisms of Disease Call, http://webarchive.nationalarchives.gov.uk/20120104105854/http://www.mrc.ac.uk/consumption/groups/public/documents/content/mrc008371.pdf

10. Takeuchi T, Hayashi M, Tamita T, Nomura Y, Kojima N, Mitani A, Takeda T, Hitaka K, Kato Y, Kamitani M et al.. (2022) Discovery of Aryloxyphenyl-Heptapeptide Hybrids as Potent and Selective Matrix Metalloproteinase-2 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem, 65 (12): 8493-8510. [PMID:35687819]

11. Taylor SJ, Abeywardane A, Liang S, Muegge I, Padyana AK, Xiong Z, Hill-Drzewi M, Farmer B, Li X, Collins B et al.. (2011) Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13. J Med Chem, 54 (23): 8174-87. [PMID:22017539]

12. Tuccinardi T, Martinelli A, Nuti E, Carelli P, Balzano F, Uccello-Barretta G, Murphy G, Rossello A. (2006) Amber force field implementation, molecular modelling study, synthesis and MMP-1/MMP-2 inhibition profile of (R)- and (S)-N-hydroxy-2-(N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanamides. Bioorg Med Chem, 14 (12): 4260-76. [PMID:16483784]

13. Verma RP, Hansch C. (2007) Matrix metalloproteinases (MMPs): chemical-biological functions and (Q)SARs. Bioorg Med Chem, 15 (6): 2223-68. [PMID:17275314]

14. Wu Y, Li J, Wu J, Morgan P, Xu X, Rancati F, Vallese S, Raveglia L, Hotchandani R, Fuller N et al.. (2012) Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD). Bioorg Med Chem Lett, 22 (1): 138-43. [PMID:22153340]

15. Xue CB, Voss ME, Nelson DJ, Duan JJ, Cherney RJ, Jacobson IC, He X, Roderick J, Chen L, Corbett RL et al.. (2001) Design, synthesis, and structure-activity relationships of macrocyclic hydroxamic acids that inhibit tumor necrosis factor alpha release in vitro and in vivo. J Med Chem, 44 (16): 2636-60. [PMID:11472217]