Target Validation Information
Target ID T54156
Target Name MMP-9
Target Type
Clinical Trial
Drug Potency against Target BB-3644 Drug Info IC50 = 70 nM [552497]
Methotrexate gamma-L-phenylalaninehydroxamic acid Drug Info IC50 = 15000 nM [528548]
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl) Drug Info IC50 = 5660 nM [529102]
IK-682 Drug Info Ki = 10340 nM [526446]
BMS 275291 Drug Info IC50 = 27 nM [552278]
2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid Drug Info IC50 = 10005 nM [528153]
RS-130830 Drug Info Ki = 0.55 nM [527412]
Tanomastat Drug Info Ki = 301 nM [552207]
4-amino-3-(4-(hexyloxy)phenyl)-4-oxobutanoic acid Drug Info IC50 = 160 nM [529392]
SC-44463 Drug Info Ki < 1 nM [526154]
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione Drug Info IC50 = 330 nM [526040]
5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione Drug Info IC50 = 14000 nM [526040]
Marimastat Drug Info IC50 = 0.85 nM [552453]
N-hydroxy-2,3-bis(phenylsulfonamido)propanamide Drug Info Ki = 227 nM [529443]
CIPEMASTAT Drug Info Ki = 59 nM [525693]
Ro-37-9790 Drug Info IC50 = 10.4 nM
UK-356618 Drug Info IC50 = 840 nM [526680]
PG-530742 Drug Info Complete Inhibition = 150 ng/mL [536172]
MMI270 Drug Info IC50 = 10 nM [525533]
CIPEMASTAT Drug Info IC50 = 59 nM
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide Drug Info IC50 = 690 nM [530402]
5-Methyl-5-phenyl-pyrimidine-2,4,6-trione Drug Info IC50 = 11000 nM [526040]
2-(biphenyl-4-ylsulfonamido)pentanedioic acid Drug Info IC50 = 14000 nM [529392]
Curcumin Drug Info IC50 = 8500 nM [529906]
Prinomastat Drug Info IC50 = 0.26 nM [552497]
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid Drug Info IC50 = 3600 nM [527972]
(+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid Drug Info IC50 = 16500 nM [530333]
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid Drug Info IC50 = 7300 nM [530402]
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione Drug Info IC50 = 696 nM [526040]
SR-973 Drug Info Ki = 5 nM [528025]
ILOMASTAT Drug Info IC50 = 0.6 nM [529683]
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide Drug Info IC50 = 7700 nM [530402]
3-(4-Phenylethynylbenzoyl)nonanoic acid Drug Info IC50 = 5410 nM [527972]
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide Drug Info IC50 = 1410 nM [529102]
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione Drug Info IC50 = 863 nM [526040]
RO-319790 Drug Info IC50 = 12 nM [534791]
Action against Disease Model Neovastat Neovastat prevented the degradation of osteoid-like radiolabeled extracellular matrices which was induced by incubation of h uMan SaOS-2 osteoblast-like cells with MDA-MB-231 cells. Moreover, Neovastat was demonstrated to inhibit the gelatinolytic activity of matrix metalloproteinase (MMP)-9 expressed by MDA-MB-231 cells [535341] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Reduced respiratory failure and lung enlargement induced by IL13, increased BAL leukocyte n uMbers; Reduced alveolar bronchiolization after bleomycin insult; Decreased peribronchial cell infiltration and BAL lymphocytes after allergic challenge, decreased carbachol hyperresponsiveness; Increased BAL-cell recruitment after allergic challenge; Decreased lung injury by immune complexes; Decreased obliterative airway disease, increased T-cell alloreactivity; Reduced inflammatory cell influx to BAL fluid in asthma; Protection and reduced hepatocyte apoptosis and necrosis in TNF-induced hepatitis; Impaired PMN infiltration 6 hours after zymosan peritonitis induction; Enhanced early vascular permeability by zymosan peritonitis; Reduced resistance against Escherichia coli peritonitis, reduced leukocyte recruitment; Decreased dextran-sulphate-induced colitis; Decreased immune-complex-induced arthritis; Increased bacterial arthritis, decreased bacterial clearance; Spontaneous delayed growth-plate angiogenesis and apoptosis of hypertrophic chondrocytes; Reduced incidence of induced chondrodermatitis; Increased collagenase-induced brain haemorrhage and injury; Reduced remyelination after tra uMa of spinal cord; Spontaneous deficient myelination of corpus callos uM, fewer oligodendrocytes; Reduced EAE in young mice; Reduced ischaemic lesion vol uMe after permanent focal ischaemia; Reduced survival of Sod1-knockout mice [552497]
References
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Ref 528548Bioorg Med Chem. 2007 Feb 1;15(3):1266-74. Epub 2006 Nov 14.Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs.
Ref 529102Bioorg Med Chem. 2008 Jan 1;16(1):530-5. Epub 2007 Sep 14.Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation.
Ref 526446J Med Chem. 2002 Nov 7;45(23):4954-7.Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structure-activity relationships.
Ref 552278Inhibition of angiogenesis and metastasis in two murine models by the matrix metalloproteinase inhibitor, BMS-275291. Cancer Res. 2001 Dec 1;61(23):8480-5.
Ref 535341The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol. 2002 Feb;20(2):299-303.
Ref 528153Bioorg Med Chem Lett. 2006 Jun 15;16(12):3096-100. Epub 2006 May 2.Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors.
Ref 527412Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13).
Ref 552207BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. Clin Cancer Res. 1999 Nov;5(11):3603-7.
Ref 529392Bioorg Med Chem. 2009 Feb 1;17(3):1101-8. Epub 2008 Mar 8.Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study.
Ref 526154J Med Chem. 2001 Oct 11;44(21):3347-50.Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors.
Ref 526040Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.
Ref 526040Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.
Ref 552453The evolution of the matrix metalloproteinase inhibitor drug discovery program at abbott laboratories. Curr Top Med Chem. 2004;4(12):1255-67.
Ref 529443Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7. Epub 2008 Apr 16.Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors.
Ref 525693J Med Chem. 2000 Feb 10;43(3):305-41.Protease inhibitors: current status and future prospects.
Ref 526680J Med Chem. 2003 Jul 31;46(16):3514-25.A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers.
Ref 536172Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2522-7. Epub 2006 Jan 20.
Ref 525533Bioorg Med Chem Lett. 1999 Jun 21;9(12):1691-6.Picking the S1, S1' and S2' pockets of matrix metalloproteinases. A niche for potent acyclic sulfonamide inhibitors.
Ref 530402J Med Chem. 2009 Oct 22;52(20):6347-61.Design, synthesis, biological evaluation, and NMR studies of a new series of arylsulfones as selective and potent matrix metalloproteinase-12 inhibitors.
Ref 526040Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.
Ref 529392Bioorg Med Chem. 2009 Feb 1;17(3):1101-8. Epub 2008 Mar 8.Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study.
Ref 529906Bioorg Med Chem. 2009 Feb 1;17(3):1290-6. Epub 2009 Jan 6.Synthesis and biological evaluation of curcuminoid pyrazoles as new therapeutic agents in inflammatory bowel disease: effect on matrix metalloproteinases.
Ref 552497Recent developments in the design of specific Matrix Metalloproteinase inhibitors aided by structural and computational studies. Curr Pharm Des. 2005;11(3):295-322.
Ref 527972J Med Chem. 2006 Jan 26;49(2):456-8.Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids.
Ref 530333Bioorg Med Chem Lett. 2009 Oct 1;19(19):5760-3. Epub 2009 Aug 6.The identification of beta-hydroxy carboxylic acids as selective MMP-12 inhibitors.
Ref 530402J Med Chem. 2009 Oct 22;52(20):6347-61.Design, synthesis, biological evaluation, and NMR studies of a new series of arylsulfones as selective and potent matrix metalloproteinase-12 inhibitors.
Ref 526040Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.
Ref 528025Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. Epub 2006 Feb 10.Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors.
Ref 529683Bioorg Med Chem. 2008 Sep 15;16(18):8745-59. Epub 2008 Jul 20.Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with improved selectivity.
Ref 530402J Med Chem. 2009 Oct 22;52(20):6347-61.Design, synthesis, biological evaluation, and NMR studies of a new series of arylsulfones as selective and potent matrix metalloproteinase-12 inhibitors.
Ref 527972J Med Chem. 2006 Jan 26;49(2):456-8.Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids.
Ref 529102Bioorg Med Chem. 2008 Jan 1;16(1):530-5. Epub 2007 Sep 14.Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation.
Ref 526040Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.
Ref 534791Bioorg Med Chem Lett. 1998 May 19;8(10):1163-8.The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases.

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