General Information of Drug Therapeutic Target (DTT) (ID: TTXZ0KQ)

DTT Name Matrix metalloproteinase-12 (MMP-12)
Synonyms Macrophage metalloelastase; Macrophage elastase; MME; ME; HME
Gene Name MMP12
DTT Type
Clinical trial target
[1]
BioChemical Class
Peptidase
UniProt ID
MMP12_HUMAN
TTD ID
T03500
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.4.24.65
Sequence
MKFLLILLLQATASGALPLNSSTSLEKNNVLFGERYLEKFYGLEINKLPVTKMKYSGNLM
KEKIQEMQHFLGLKVTGQLDTSTLEMMHAPRCGVPDVHHFREMPGGPVWRKHYITYRINN
YTPDMNREDVDYAIRKAFQVWSNVTPLKFSKINTGMADILVVFARGAHGDFHAFDGKGGI
LAHAFGPGSGIGGDAHFDEDEFWTTHSGGTNLFLTAVHEIGHSLGLGHSSDPKAVMFPTY
KYVDINTFRLSADDIRGIQSLYGDPKENQRLPNPDNSEPALCDPNLSFDAVTTVGNKIFF
FKDRFFWLKVSERPKTSVNLISSLWPTLPSGIEAAYEIEARNQVFLFKDDKYWLISNLRP
EPNYPKSIHSFGFPNFVKKIDAAVFNPRFYRTYFFVDNQYWRYDERRQMMDPGYPKLITK
NFQGIGPKIDAVFYSKNKYYYFFQGSNQFEYDFLLQRITKTLKSNSWFGC
Function
Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3. May be involved in tissue injury and remodeling.
Reactome Pathway
Degradation of the extracellular matrix (R-HSA-1474228 )
Collagen degradation (R-HSA-1442490 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
FP-025 DMH1NXO Asthma CA23 Phase 1 [1]
Neovastat DMXTYWJ Non-small-cell lung cancer 2C25.Y Phase 1 [2]
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3 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PMID29130358-Compound-Figure17(10) DMVA15O N. A. N. A. Patented [3]
PMID29130358-Compound-Figure17(11) DMSZA9L N. A. N. A. Patented [3]
PMID29130358-Compound-Figure17(12) DMML4PA N. A. N. A. Patented [3]
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3 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AZD1236 DML3RSF Chronic obstructive pulmonary disease CA22 Discontinued in Phase 2 [4]
GM6001 DM7V9CT Corneal ulcer 9A76 Discontinued in Phase 2 [5]
V85546 DMLFMSY Inflammation 1A00-CA43.1 Discontinued in Phase 1 [6]
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34 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid DMSN7GJ Discovery agent N.A. Investigative [7]
2-(2-(biphenyl-4-yl)ethylsulfinyl)acetic acid DMDR50V Discovery agent N.A. Investigative [7]
2-(2-(biphenyl-4-yl)ethylsulfonyl)acetic acid DM95B4J Discovery agent N.A. Investigative [7]
2-(2-(biphenyl-4-yl)ethylthio)acetic acid DMBZIUC Discovery agent N.A. Investigative [7]
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide DMCNV5J Discovery agent N.A. Investigative [8]
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid DMQDPHT Discovery agent N.A. Investigative [5]
3-(4-Phenylethynylbenzoyl)nonanoic acid DMXL0J5 Discovery agent N.A. Investigative [5]
3-Benzenesulfonyl-heptanoic acid hydroxyamide DM7XDCF Discovery agent N.A. Investigative [9]
3-Cyclohexanesulfonyl-heptanoic acid hydroxyamide DMJSOTE Discovery agent N.A. Investigative [9]
4-(4-(dec-1-ynyl)phenyl)-4-oxobutanoic acid DM6KIG0 Discovery agent N.A. Investigative [5]
5-(3'-cyanobiphenyl-4-yl)-3-hydroxypentanoic acid DMPC9DV Discovery agent N.A. Investigative [7]
5-(4'-cyanobiphenyl-4-yl)-3-hydroxypentanoic acid DMTDNX3 Discovery agent N.A. Investigative [7]
5-(biphenyl-4-yl)-3-methoxypentanoic acid DMJAG7M Discovery agent N.A. Investigative [7]
5-(biphenyl-4-yl)-3-oxopentanoic acid DMQKU9H Discovery agent N.A. Investigative [7]
Acetate Ion DMD08RH Discovery agent N.A. Investigative [10]
AGELADINE A DMOJ3CW Discovery agent N.A. Investigative [11]
CP-271485 DMGN38F Discovery agent N.A. Investigative [10]
MMP-408 DMVCNBH Chronic obstructive pulmonary disease CA22 Investigative [12]
N-(biphenyl-4-ylsulfonyl)-D-leucine DMHPITZ Discovery agent N.A. Investigative [13]
N-(dibenzo[b,d]thiophen-3-ylsulfonyl)-L-valine DMI245K Discovery agent N.A. Investigative [13]
N-Hydroxy-2-(4-methoxy-benzenesulfonyl)benzamide DM56P1I Discovery agent N.A. Investigative [8]
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide DM4VADN Discovery agent N.A. Investigative [8]
N-oxo-2-(phenylsulfonylamino)ethanamide DMQ84J7 Discovery agent N.A. Investigative [13]
N-oxo-2-[(4-phenylphenyl)sulfonylamino]ethanamide DMHTI5X Discovery agent N.A. Investigative [13]
N-[(4-methoxyphenyl)sulfonyl]-D-alanine DMVOJFW Discovery agent N.A. Investigative [13]
PF-00356231 DMV43NF Discovery agent N.A. Investigative [14]
PMID22153340C20 DMTGVSU Discovery agent N.A. Investigative [15]
PMID24900526C1 DMEWVG8 Discovery agent N.A. Investigative [16]
PMID24900526C5 DMKTBCM Discovery agent N.A. Investigative [16]
PUP-1 DMCWT4L Chronic obstructive pulmonary disease CA22 Investigative [12]
RXP-470 DM5GIUY Arteriosclerosis BD40 Investigative [12]
RXP470.1 DMB7EGU Discovery agent N.A. Investigative [17]
WAY-644 DMNCZEQ Aortic aneurysm BD50 Investigative [12]
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid DM37C25 Discovery agent N.A. Investigative [8]
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⏷ Show the Full List of 34 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Lung cancer 2C82 Lung tissue 1.22E-106 5.08 3.56
Chronic obstructive pulmonary disease CA23 Lung tissue 2.14E-01 0.24 0.22
Chronic obstructive pulmonary disease CA23 Small airway epithelium 3.35E-06 0.91 1
Renal cancer 2C82 Kidney 2.58E-04 -0.1 -0.27
Coronary artery disease BA80-BA8Z Peripheral blood 9.19E-01 -0.03 -0.23
Asthma CA23 Nasal and bronchial airway 1.31E-06 0.62 0.65
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⏷ Show the Full List of DTT Expression Under 6 Diseases

References

1 Potential clinical implications of recent matrix metalloproteinase inhibitor design strategies. Expert Rev Proteomics. 2015;12(5):445-7.
2 Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001 Dec;28(6):620-5.
3 Gelatinase inhibitors: a patent review (2011-2017).Expert Opin Ther Pat. 2018 Jan;28(1):31-46.
4 Clinical pipeline report, company report or official report of AstraZeneca (2009).
5 Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids. J Med Chem. 2006 Jan 26;49(2):456-8.
6 Clinical pipeline report, company report or official report of Vernalis.
7 The identification of beta-hydroxy carboxylic acids as selective MMP-12 inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5760-3.
8 Design, synthesis, biological evaluation, and NMR studies of a new series of arylsulfones as selective and potent matrix metalloproteinase-12 inhib... J Med Chem. 2009 Oct 22;52(20):6347-61.
9 Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents. J Med Chem. 2000 Jun 15;43(12):2324-31.
10 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
11 Synthesis of novel ageladine A analogs showing more potent matrix metalloproteinase (MMP)-12 inhibitory activity than the natural product. Bioorg Med Chem Lett. 2009 Sep 15;19(18):5461-3.
12 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1636).
13 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
14 DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
15 Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD). Bioorg Med Chem Lett. 2012 Jan 1;22(1):138-43.
16 Target-Activated Prodrugs (TAPs) for the Autoregulated Inhibition of MMP12. ACS Med Chem Lett. 2012 Jul 14;3(8):653-7.
17 Molecular determinants of a selective matrix metalloprotease-12 inhibitor: insights from crystallography and thermodynamic studies. J Med Chem. 2013 Feb 14;56(3):1149-59.