MMPs as therapeutic targets--still a viable option?
Matrix metalloproteinases (MMPs) appear to be ideal drug targets--they are disease-associated, extracellular enzymes with a dependence on zinc for activity. This apparently straightforward target, however, is much more complex than initially realized. Although disease associated, the roles for particular enzymes may be healing rather than harmful making broad-spectrum inhibition unwise; targeting the catalytic zinc with specificity is difficult, since other related proteases as well as non-related proteins can be affected by some chelating groups. While the failure of early-generation MMP inhibitors dampened enthusiasm for this type of drug, there has recently been a wealth of studies examining the basic biology of MMPs which will greatly inform new drug trials in this field.
Fingleton
Barbara
B
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA. Barbara.fingleton@vanderbilt.edu
D000818:Animals; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology; D008659:Metabolic Diseases / Q000188:drug therapy*; D023421:Models, Animal; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases
Front Biosci. 2006;11:479-91
16146745
Front Biosci. 2006;11:529-43
16146751
J Invest Dermatol. 2006 Feb;126(2):486-96
16374453
Cardiovasc Res. 2006 Feb 15;69(3):677-87
16413004
Cardiovasc Res. 2006 Feb 15;69(3):585-94
16426591
Clin Chim Acta. 2006 Mar;365(1-2):183-7
16168399
Clin Cancer Res. 2006 Mar 1;12(5):1556-63
16533781
Br J Cancer. 2006 Apr 10;94(7):941-6
16538215
PLoS Med. 2006 Apr;3(4):e100
16509766
Cancer Metastasis Rev. 2006 Mar;25(1):9-34
16680569
Proc Am Thorac Soc. 2006 Jun;3(4):383-8
16738205
Cancer Res. 2006 Jun 15;66(12):6149-55
16778188
Cancer Res. 2006 Aug 15;66(16):7968-75
16912171
Pharmacol Ther. 2006 Oct;112(1):71-105
16714062
Clin Sci (Lond). 2007 Jan;112(1):43-9
16939410
Nat Immunol. 2002 Apr;3(4):347-53
11887181
Science. 2002 Mar 29;295(5564):2387-92
11923519
Nat Rev Cancer. 2002 Mar;2(3):161-74
11990853
J Am Coll Cardiol. 2002 Jun 5;39(11):1852-8
12039502
Circ Res. 2002 Nov 1;91(9):852-9
12411401
J Biol Chem. 2002 Dec 20;277(51):49598-604
12393861
Am J Clin Oncol. 2002 Dec;25(6 Suppl 1):S3-9
12562045
J Nucl Cardiol. 2003 Jan-Feb;10(1):77-86
12569335
Anticancer Res. 2003 Jan-Feb;23(1B):639-45
12680160
Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):535-42
12615660
Inflamm Res. 2003 Mar;52(3):95-100
12755372
Br J Cancer. 2003 May 6;88(9):1445-52
12778076
Cancer Metastasis Rev. 2003 Jun-Sep;22(2-3):177-203
12784996
Expert Opin Ther Targets. 2003 Jun;7(3):385-97
12783574
Arthritis Rheum. 2003 Jun;48(6):1742-9
12794843
Nat Rev Genet. 2003 Jul;4(7):544-58
12838346
Stroke. 2003 Aug;34(8):2025-30
12855824
Circulation. 2003 Sep 16;108(11):1375-81
12939223
Cancer Biol Ther. 2003 Jul-Aug;2(4 Suppl 1):S134-9
14508091
Nat Neurosci. 2003 Oct;6(10):1064-71
14502291
Nat Genet. 2003 Nov;35(3):252-7
14517555
Anticancer Drugs. 2003 Nov;14(10):773-8
14597870
Cell Mol Biol (Noisy-le-grand). 2003 Sep;49(6):875-84
14656045
Am J Physiol Heart Circ Physiol. 2004 Jan;286(1):H1-H10
14684355
Heart Fail Rev. 2004 Jan;9(1):7-19
14739764
Genes Immun. 2004 Mar;5(2):147-9
14712311
Blood. 2004 Apr 1;103(7):2610-6
14630814
Clin Cancer Res. 2004 Mar 15;10(6):1971-5
15041714
Curr Med Res Opin. 2004 Apr;20(4):419-32
15119978
Clin Exp Metastasis. 1999 Mar;17(2):177-81
10411111
Nat Med. 1999 Oct;5(10):1135-42
10502816
Cell. 1999 Oct 1;99(1):81-92
10520996
FASEB J. 2004 Nov;18(14):1682-91
15522913
Development. 2004 Dec;131(23):5883-95
15539485
J Cell Biol. 2004 Nov 22;167(4):769-81
15557125
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17192-7
15563592
J Clin Invest. 2000 Jun;105(11):1641-9
10841523
Circulation. 2000 Jun 27;101(25):2962-7
10869270
Science. 2000 Aug 18;289(5482):1202-6
10947989
Nat Cell Biol. 2000 Oct;2(10):737-44
11025665
Cell. 2000 Oct 27;103(3):481-90
11081634
Matrix Biol. 2000 Dec;19(7):623-9
11102751
J Cereb Blood Flow Metab. 2000 Dec;20(12):1681-9
11129784
Cell. 1998 May 1;93(3):411-22
9590175
Hepatology. 1998 Oct;28(4):986-93
9755235
Int J Cancer. 1998 Nov 23;78(5):629-35
9808534
Curr Pharm Des. 2007;13(3):333-46
17313364
ChemMedChem. 2007 Feb;2(2):152-71
17163561
Mol Microbiol. 2007 Apr;64(1):94-110
17376075
Curr Probl Pediatr Adolesc Health Care. 2007 Apr;37(4):118-35
17434008
J Surg Res. 2007 May 15;139(2):292-307
17292415
Nat Rev Drug Discov. 2007 May;6(5):349-56
17431406
Hum Mol Genet. 2007 May 1;16(9):1113-23
17400654
Cancer Metastasis Rev. 2007 Dec;26(3-4):717-24
17717634
J Clin Invest. 2000 Jan;105(2):133-41
10642591
J Clin Invest. 2000 Jan;105(2):143-50
10642592
Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4052-7
10737763
Cancer. 2001 Apr 1;91(7):1277-83
11283927
J Surg Res. 2001 Aug;99(2):245-52
11469893
Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1440-5
11557669
Cancer Res. 2001 Dec 1;61(23):8480-5
11731431
Sarcoidosis Vasc Diffuse Lung Dis. 2004 Mar;21(1):19-24
15127970
Arthritis Res Ther. 2004;6(3):R199-207
15142265
Treat Respir Med. 2004;3(1):17-27
15174890
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10000-5
15220480
Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1479-84
15191941
Drug Resist Updat. 2004 Jun;7(3):195-208
15296861
Curr Biol. 2004 Sep 7;14(17):1531-9
15341739
J Clin Invest. 2004 Sep;114(5):623-33
15343380
Int J Dev Biol. 2004;48(5-6):411-24
15349816
Cancer Res. 2004 Oct 1;64(19):6965-72
15466188
Mol Biol Cell. 1995 Jul;6(7):851-69
7579699
Cell. 1997 Mar 21;88(6):801-10
9118223
Science. 1997 Sep 26;277(5334):2002-4
9302297
Endocrinology. 1997 Nov;138(11):4902-11
9348221
Cancer Res. 1998 Mar 1;58(5):1048-51
9500469
J Vasc Surg. 1998 Dec;28(6):1082-93
9845660
Cancer Res. 1998 Dec 1;58(23):5321-5
9850057
J Immunol. 1998 Dec 15;161(12):6845-52
9862716
Thorax. 1998 Oct;53(10):815-7
10193364
Science. 1999 Apr 30;284(5415):808-12
10221914
Circulation. 1999 Jun 1;99(21):2717-9
10351963
Physiol Rev. 2005 Jan;85(1):1-31
15618476
Inflamm Res. 2005 Jan;54(1):31-6
15723202
J Clin Invest. 2005 Mar;115(3):599-609
15711638
J Clin Oncol. 2005 Apr 20;23(12):2831-9
15837997
Glia. 2005 Jun;50(4):329-39
15846802
Curr Opin Cardiol. 2005 May;20(3):211-6
15861009
Curr Med Res Opin. 2005 Apr;21(4):587-94
15899108
Bioorg Med Chem Lett. 2005 Aug 15;15(16):3787-90
16002291
Eur J Vasc Endovasc Surg. 2005 Sep;30(3):259-62
16009575
Curr Drug Targets Inflamm Allergy. 2005 Jun;4(3):363-75
16101546
Oncology. 2005;69(1):35-43
16088233