Target Validation Information | |||||
---|---|---|---|---|---|
TTD ID | T68251 | ||||
Target Name | Matrix metalloproteinase-2 (MMP-2) | ||||
Type of Target |
Successful |
||||
Drug Potency against Target | BB-3644 | Drug Info | IC50 = 80 nM | [24] | |
BMS 275291 | Drug Info | IC50 = 39 nM | [23] | ||
Marimastat | Drug Info | Ki = 6 nM | [25] | ||
PG-530742 | Drug Info | Complete Inhibition = 150 ng/mL | [21] | ||
Tanomastat | Drug Info | Ki = 11 nM | [22] | ||
(+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid | Drug Info | IC50 = 4520 nM | [16] | ||
2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid | Drug Info | IC50 = 792 nM | [11] | ||
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide | Drug Info | IC50 = 1300 nM | [18] | ||
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid | Drug Info | IC50 = 440 nM | [8] | ||
3-(4-Phenylethynylbenzoyl)nonanoic acid | Drug Info | IC50 = 1660 nM | [8] | ||
4-(4-(dec-1-ynyl)phenyl)-4-oxobutanoic acid | Drug Info | IC50 = 3070 nM | [8] | ||
5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione | Drug Info | IC50 = 9000 nM | [3] | ||
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 898 nM | [3] | ||
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 868 nM | [3] | ||
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione | Drug Info | IC50 = 1300 nM | [3] | ||
BB-1101 | Drug Info | IC50 = 1.8 nM | [19] | ||
CIPEMASTAT | Drug Info | Ki = 154 nM | [2] | ||
CIPEMASTAT | Drug Info | IC50 = 7 nM | |||
Cis-2-aminocyclohexylcarbamoylphosphonic acid | Drug Info | IC50 = 4000 nM | [13] | ||
Clinopodic acid C | Drug Info | IC50 = 3260 nM | [17] | ||
Epigallocatechin gallate | Drug Info | IC50 = 9600 nM | [15] | ||
GM6001 | Drug Info | IC50 = 0.4 nM | [14] | ||
IK-862 | Drug Info | Ki = 2050 nM | [4] | ||
L-696418 | Drug Info | Ki = 200 nM | |||
Lithospermic acid | Drug Info | IC50 = 10200 nM | [17] | ||
MMI270 | Drug Info | IC50 = 15 nM | [1] | ||
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide | Drug Info | IC50 = 1200 nM | [18] | ||
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide | Drug Info | IC50 = 200 nM | [12] | ||
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl) | Drug Info | IC50 = 590 nM | [12] | ||
PD-169469 | Drug Info | IC50 = 4 nM | [9] | ||
PNU-107859 | Drug Info | Ki = 3000 nM | [6] | ||
Ro-37-9790 | Drug Info | IC50 = 4.9 nM | |||
RS-130830 | Drug Info | Ki = 0.22 nM | [7] | ||
SC-44463 | Drug Info | IC50 = 6 nM | [5] | ||
SR-973 | Drug Info | Ki = 7 nM | [10] | ||
UK-356618 | Drug Info | IC50 = 1790 nM | [5] | ||
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid | Drug Info | IC50 = 510 nM | [18] | ||
Action against Disease Model | Neovastat | Drug Info | 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. | [20] | |
References | |||||
REF 1 | Picking the S1, S1' and S2' pockets of matrix metalloproteinases. A niche for potent acyclic sulfonamide inhibitors. Bioorg Med Chem Lett. 1999 Jun 21;9(12):1691-6. | ||||
REF 2 | Protease inhibitors: current status and future prospects. J Med Chem. 2000 Feb 10;43(3):305-41. | ||||
REF 3 | Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72. | ||||
REF 4 | Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structu... J Med Chem. 2002 Nov 7;45(23):4954-7. | ||||
REF 5 | A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers. J Med Chem. 2003 Jul 31;46(16):3514-25. | ||||
REF 6 | A molecular basis for the selectivity of thiadiazole urea inhibitors with stromelysin-1 and gelatinase-A from generalized born molecular dynamics s... J Med Chem. 2004 Jun 3;47(12):3065-74. | ||||
REF 7 | Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6. | ||||
REF 8 | 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. | ||||
REF 9 | Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates. J Med Chem. 2006 Feb 9;49(3):923-31. | ||||
REF 10 | Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors. Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. | ||||
REF 11 | Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors. Bioorg Med Chem Lett. 2006 Jun 15;16(12):3096-100. | ||||
REF 12 | Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation. Bioorg Med Chem. 2008 Jan 1;16(1):530-5. | ||||
REF 13 | Carbamoylphosphonate matrix metalloproteinase inhibitors 6: cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastatic mat... J Med Chem. 2008 Mar 13;51(5):1406-14. | ||||
REF 14 | Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with i... Bioorg Med Chem. 2008 Sep 15;16(18):8745-59. | ||||
REF 15 | Regioselective synthesis of methylated epigallocatechin gallate via nitrobenzenesulfonyl (Ns) protecting group. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4171-4. | ||||
REF 16 | The identification of beta-hydroxy carboxylic acids as selective MMP-12 inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5760-3. | ||||
REF 17 | Matrix metalloproteinase-2 inhibitors from Clinopodium chinense var. parviflorum. J Nat Prod. 2009 Aug;72(8):1379-84. | ||||
REF 18 | 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. | ||||
REF 19 | Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution. Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8. | ||||
REF 20 | Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001 Dec;28(6):620-5. | ||||
REF 21 | Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart fail... Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2522-7. | ||||
REF 22 | BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. Clin Cancer Res. 1999 Nov;5(11):3603-7. | ||||
REF 23 | 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 24 | 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 25 | BCL-2 family antagonists for cancer therapy. Nat Rev Drug Discov. 2008 Dec;7(12):989-1000. | ||||
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