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 | [1] | |
Methotrexate gamma-L-phenylalaninehydroxamic acid | Drug Info | IC50 = 15000 nM | [2] | ||
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl) | Drug Info | IC50 = 5660 nM | [3] | ||
IK-682 | Drug Info | Ki = 10340 nM | [4] | ||
BMS 275291 | Drug Info | IC50 = 27 nM | [5] | ||
2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid | Drug Info | IC50 = 10005 nM | [6] | ||
RS-130830 | Drug Info | Ki = 0.55 nM | [7] | ||
Tanomastat | Drug Info | Ki = 301 nM | [8] | ||
4-amino-3-(4-(hexyloxy)phenyl)-4-oxobutanoic acid | Drug Info | IC50 = 160 nM | [9] | ||
SC-44463 | Drug Info | Ki < 1 nM | [10] | ||
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 330 nM | [11] | ||
5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione | Drug Info | IC50 = 14000 nM | [11] | ||
Marimastat | Drug Info | IC50 = 0.85 nM | [12] | ||
N-hydroxy-2,3-bis(phenylsulfonamido)propanamide | Drug Info | Ki = 227 nM | [13] | ||
CIPEMASTAT | Drug Info | Ki = 59 nM | [14] | ||
Ro-37-9790 | Drug Info | IC50 = 10.4 nM | |||
UK-356618 | Drug Info | IC50 = 840 nM | [15] | ||
PG-530742 | Drug Info | Complete Inhibition = 150 ng/mL | [16] | ||
MMI270 | Drug Info | IC50 = 10 nM | [17] | ||
CIPEMASTAT | Drug Info | IC50 = 59 nM | |||
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide | Drug Info | IC50 = 690 nM | [18] | ||
5-Methyl-5-phenyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 11000 nM | [11] | ||
2-(biphenyl-4-ylsulfonamido)pentanedioic acid | Drug Info | IC50 = 14000 nM | [9] | ||
Curcumin | Drug Info | IC50 = 8500 nM | [19] | ||
Prinomastat | Drug Info | IC50 = 0.26 nM | [1] | ||
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid | Drug Info | IC50 = 3600 nM | [20] | ||
(+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid | Drug Info | IC50 = 16500 nM | [21] | ||
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid | Drug Info | IC50 = 7300 nM | [18] | ||
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 696 nM | [11] | ||
SR-973 | Drug Info | Ki = 5 nM | [22] | ||
ILOMASTAT | Drug Info | IC50 = 0.6 nM | [23] | ||
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide | Drug Info | IC50 = 7700 nM | [18] | ||
3-(4-Phenylethynylbenzoyl)nonanoic acid | Drug Info | IC50 = 5410 nM | [20] | ||
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide | Drug Info | IC50 = 1410 nM | [3] | ||
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 863 nM | [11] | ||
RO-319790 | Drug Info | IC50 = 12 nM | [24] | ||
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 | [25] | 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 | [1] | |||
References | |||||
REF 1 | Recent developments in the design of specific Matrix Metalloproteinase inhibitors aided by structural and computational studies. Curr Pharm Des. 2005;11(3):295-322. | ||||
REF 2 | Bioorg Med Chem. 2007 Feb 1;15(3):1266-74. Epub 2006 Nov 14.Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs. | ||||
REF 3 | Bioorg 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 4 | J 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 5 | Inhibition 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 6 | Bioorg 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 7 | Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). | ||||
REF 8 | BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. Clin Cancer Res. 1999 Nov;5(11):3603-7. | ||||
REF 9 | Bioorg 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 10 | J 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 11 | Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. | ||||
REF 12 | The evolution of the matrix metalloproteinase inhibitor drug discovery program at abbott laboratories. Curr Top Med Chem. 2004;4(12):1255-67. | ||||
REF 13 | Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7. Epub 2008 Apr 16.Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors. | ||||
REF 14 | J Med Chem. 2000 Feb 10;43(3):305-41.Protease inhibitors: current status and future prospects. | ||||
REF 15 | J 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 16 | Selective 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 17 | Bioorg 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 18 | J 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 19 | Bioorg 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 20 | J 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 21 | Bioorg 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 22 | Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. Epub 2006 Feb 10.Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors. | ||||
REF 23 | Bioorg 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 24 | Bioorg 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. | ||||
REF 25 | The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol. 2002 Feb;20(2):299-303. | ||||
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