Target Validation Information | |||||
---|---|---|---|---|---|
Target ID | T68251 | ||||
Target Name | 72 kDa type IV collagenase | ||||
Target Type | Successful |
||||
Drug Potency against Target | Tanomastat | Drug Info | Ki = 11 nM | [552207] | |
UK-356618 | Drug Info | IC50 = 1790 nM | [526680] | ||
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl) | Drug Info | IC50 = 590 nM | [529102] | ||
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide | Drug Info | IC50 = 1200 nM | [530402] | ||
PNU-107859 | Drug Info | Ki = 3000 nM | [527091] | ||
(+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid | Drug Info | IC50 = 4520 nM | [530333] | ||
BB-3644 | Drug Info | IC50 = 80 nM | [552497] | ||
2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid | Drug Info | IC50 = 792 nM | [528153] | ||
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 898 nM | [526040] | ||
SR-973 | Drug Info | Ki = 7 nM | [528025] | ||
IK-682 | Drug Info | Ki = 2050 nM | [526446] | ||
Ro-37-9790 | Drug Info | IC50 = 4.9 nM | |||
L-696418 | Drug Info | Ki = 200 nM | |||
CIPEMASTAT | Drug Info | Ki = 154 nM | [525693] | ||
Marimastat | Drug Info | Ki = 6 nM | [552892] | ||
ILOMASTAT | Drug Info | IC50 = 0.4 nM | [529683] | ||
BMS 275291 | Drug Info | IC50 = 39 nM | [552278] | ||
Cis-2-aminocyclohexylcarbamoylphosphonic acid | Drug Info | IC50 = 4000 nM | [529297] | ||
3-(4-Phenylethynylbenzoyl)nonanoic acid | Drug Info | IC50 = 1660 nM | [527972] | ||
SC-44463 | Drug Info | IC50 = 6 nM | [526680] | ||
RS-130830 | Drug Info | Ki = 0.22 nM | [527412] | ||
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 1300 nM | [526040] | ||
4-(4-(dec-1-ynyl)phenyl)-4-oxobutanoic acid | Drug Info | IC50 = 3070 nM | [527972] | ||
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide | Drug Info | IC50 = 200 nM | [529102] | ||
Clinopodic acid C | Drug Info | IC50 = 3260 nM | [530340] | ||
5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione | Drug Info | IC50 = 9000 nM | [526040] | ||
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 868 nM | [526040] | ||
PD-169469 | Drug Info | IC50 = 4 nM | [527998] | ||
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid | Drug Info | IC50 = 510 nM | [530402] | ||
Lithospermic acid | Drug Info | IC50 = 10200 nM | [530340] | ||
BB-1101 | Drug Info | IC50 = 1.8 nM | [534793] | ||
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide | Drug Info | IC50 = 1300 nM | [530402] | ||
EPIGALOCATECHIN GALLATE | Drug Info | IC50 = 9600 nM | [530210] | ||
PG-530742 | Drug Info | Complete Inhibition = 150 ng/mL | [536172] | ||
CIPEMASTAT | Drug Info | IC50 = 7 nM | |||
MMI270 | Drug Info | IC50 = 15 nM | [525533] | ||
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid | Drug Info | IC50 = 440 nM | [527972] | ||
Action against Disease Model | Neovastat | Neovastat has a marked inhibitory effect on the formation of blood vessels in the chicken embryo vascularization assay (EVT) and endothelial cell proliferation. In vivo experiments showed that oral administration of Neovastat blocks the formation of blood vessels in Matrigel implants containing basic fibroblast growth factor (bFGF). The antiangiogenic activity of Neovastat was found to be associated with two mechanisms of action. In addition to the inhibition of the matrix metalloproteinase activities (MMP-2, MMP-9, and MMP-12), Neovastat inhibits vascular endothelial growth factor (VEGF) binding to endothelial cells, VEGF-dependent tyrosine phosphorylation, and VEGF-induced vascular permeability in mice. Neovastat was also found to have a significant antit uMor activity. Oral administration of Neovastat in mice with subcutaneous grafted breast cancer (DA3) cells showed a significant reduction in t uMor vol uMe. Neovastat also decreased the n uMber of lung metastases in the Lewis lung carcinoma model. | [535315] | Drug Info | |
The Effect of Target Knockout, Knockdown or Genetic Variations | Increased allergen-induced asphyxiation, reduced intral uMinal leukocytes; Increased dextran-sulphate-induced colitis; Protection and reduced hepatocyte apoptosis and necrosis in TNF-induced hepatitis; Increased immune-complex-induced arthritis; Reduced functional recovery from spinal-cord injury; Reduced EAE development | [552207] | |||
References | |||||
Ref 552207 | BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. Clin Cancer Res. 1999 Nov;5(11):3603-7. | ||||
Ref 526680 | 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 529102 | 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 530402 | 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 527091 | J Med Chem. 2004 Jun 3;47(12):3065-74.A molecular basis for the selectivity of thiadiazole urea inhibitors with stromelysin-1 and gelatinase-A from generalized born molecular dynamics simulations. | ||||
Ref 530333 | 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 552497 | 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 528153 | 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 526040 | Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. | ||||
Ref 528025 | 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 526446 | 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 525693 | J Med Chem. 2000 Feb 10;43(3):305-41.Protease inhibitors: current status and future prospects. | ||||
Ref 552892 | BCL-2 family antagonists for cancer therapy. Nat Rev Drug Discov. 2008 Dec;7(12):989-1000. doi: 10.1038/nrd2658. | ||||
Ref 529683 | 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 552278 | 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 529297 | J Med Chem. 2008 Mar 13;51(5):1406-14. Epub 2008 Feb 8.Carbamoylphosphonate matrix metalloproteinase inhibitors 6: cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastaticmatrix metalloproteinase-2 selective inhibitor--synthesis and pharmacodynamic and pharmacokinetic analysis. | ||||
Ref 527972 | 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 526680 | 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 527412 | 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 526040 | Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. | ||||
Ref 527972 | 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 529102 | 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 530340 | J Nat Prod. 2009 Aug;72(8):1379-84.Matrix metalloproteinase-2 inhibitors from Clinopodium chinense var. parviflorum. | ||||
Ref 526040 | Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. | ||||
Ref 526040 | Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. | ||||
Ref 527998 | J Med Chem. 2006 Feb 9;49(3):923-31.Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates. | ||||
Ref 530402 | 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 530340 | J Nat Prod. 2009 Aug;72(8):1379-84.Matrix metalloproteinase-2 inhibitors from Clinopodium chinense var. parviflorum. | ||||
Ref 535315 | Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001 Dec;28(6):620-5. | ||||
Ref 534793 | Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8.Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution. | ||||
Ref 530402 | 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 530210 | Bioorg Med Chem Lett. 2009 Aug 1;19(15):4171-4. Epub 2009 Jun 2.Regioselective synthesis of methylated epigallocatechin gallate via nitrobenzenesulfonyl (Ns) protecting group. | ||||
Ref 536172 | 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 525533 | 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 527972 | 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. |
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