Review Article

选择性MMP-13抑制剂:有望治疗骨性关节炎的药物

卷 27, 期 22, 2020

页: [3753 - 3769] 页: 17

弟呕挨: 10.2174/0929867326666181217153118

价格: $65

摘要

骨关节炎(OA)是一种年龄相关性退行性疾病,以慢性关节疼痛、炎症和关节软骨损伤为特征。目前,甾体类药物和非甾体类抗炎药(NSAIDS)、选择性环氧合酶-2 (COX-2)抑制剂是治疗OA的一线药物。然而,这些药物可能会导致一些心血管副作用。因此,开发新的治疗OA的药物已成为当务之急。基质金属蛋白酶-13 (Matrix metalloproteinase, MMP-13)是基质金属蛋白酶家族(Matrix metalloproteinases, MMPs)的重要成员,通过降解关节软骨和骨组织中的II型胶原而发挥重要作用。值得注意的是,MMP-13在OA患者中异常表达,而在正常成人中不表达。此外,广谱MMP抑制剂可能会导致一些疼痛和关节僵硬的副作用,在临床试验中称为肌肉骨骼综合征(MSS)。因此,开发选择性MMP-13抑制剂是治疗OA的一个潜在策略。本文综述了选择性MMP-13抑制剂的研究进展,包括锌结合和非锌结合选择性MMP-13抑制剂两个亚家族。

关键词: 骨关节炎,关节软骨,MMP-13,锌结合基,构效关系,选择性抑制剂。

« Previous
[1]
Lane, N.E.; Shidara, K.; Wise, B.L. Osteoarthritis year in review 2016: clinical. Osteoarthritis Cartilage, 2017, 25(2), 209-215.
[http://dx.doi.org/10.1016/j.joca.2016.09.025] [PMID: 28100423]
[2]
Hunter, D.J. Osteoarthritis. Best Pract. Res. Clin. Rheumatol., 2011, 25(6), 801-814.
[http://dx.doi.org/10.1016/j.berh.2011.11.008] [PMID: 22265262]
[3]
Loeser, R.F.; Goldring, S.R.; Scanzello, C.R.; Goldring, M.B. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum., 2012, 64(6), 1697-1707.
[http://dx.doi.org/10.1002/art.34453] [PMID: 22392533]
[4]
Felson, D.T.; Lawrence, R.C.; Dieppe, P.A.; Hirsch, R.; Helmick, C.G.; Jordan, J.M.; Kington, R.S.; Lane, N.E.; Nevitt, M.C.; Zhang, Y.; Sowers, M.; McAlindon, T.; Spector, T.D.; Poole, A.R.; Yanovski, S.Z.; Ateshian, G.; Sharma, L.; Buckwalter, J.A.; Brandt, K.D.; Fries, J.F. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann. Intern. Med., 2000, 133(8), 635-646.
[http://dx.doi.org/10.7326/0003-4819-133-8-200010170-00016] [PMID: 11033593]
[5]
Li, N.G.; Shi, Z.H.; Tang, Y.P.; Wang, Z.J.; Song, S.L.; Qian, L.H.; Qian, D.W.; Duan, J.A. New hope for the treatment of osteoarthritis through selective inhibition of MMP-13. Curr. Med. Chem., 2011, 18(7), 977-1001.
[http://dx.doi.org/10.2174/092986711794940905] [PMID: 21254976]
[6]
Fitzgerald, G.A. Coxibs and cardiovascular disease. N. Engl. J. Med., 2004, 351(17), 1709-1711.
[http://dx.doi.org/10.1056/NEJMp048288] [PMID: 15470192]
[7]
Steinmeyer, J.; Konttinen, Y.T. Oral treatment options for degenerative joint disease--presence and future. Adv. Drug Deliv. Rev., 2006, 58(2), 168-211.
[http://dx.doi.org/10.1016/j.addr.2006.01.007] [PMID: 16616797]
[8]
Hunter, D.J. Pharmacologic therapy for osteoarthritis--the era of disease modification. Nat. Rev. Rheumatol., 2011, 7(1), 13-22.
[http://dx.doi.org/10.1038/nrrheum.2010.178] [PMID: 21079644]
[9]
Tonge, D.P.; Pearson, M.J.; Jones, S.W. The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics. Osteoarthritis Cartilage, 2014, 22(5), 609-621.
[http://dx.doi.org/10.1016/j.joca.2014.03.004] [PMID: 24632293]
[10]
Murphy, G.; Nagase, H. Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat. Clin. Pract. Rheumatol., 2008, 4(3), 128-135.
[http://dx.doi.org/10.1038/ncprheum0727] [PMID: 18253109]
[11]
Zhang, E.; Yan, X.; Zhang, M.; Chang, X.; Bai, Z.; He, Y.; Yuan, Z. Aggrecanases in the human synovial fluid at different stages of osteoarthritis. Clin. Rheumatol., 2013, 32(6), 797-803.
[http://dx.doi.org/10.1007/s10067-013-2171-0] [PMID: 23370724]
[12]
Li, J.Y.; Ye, Q.Z. A new target for athritis: advance in the study of aggrecanase. Prog. Biochem. Biophys., 2001, 28(5), 654-657.
[13]
Sabatini, M.; Lesur, C.; Thomas, M.; Chomel, A.; Anract, P.; de Nanteuil, G.; Pastoureau, P. Effect of inhibition of matrix metalloproteinases on cartilage loss in vitro and in a guinea pig model of osteoarthritis. Arthritis Rheum., 2005, 52(1), 171-180.
[http://dx.doi.org/10.1002/art.20900] [PMID: 15641085]
[14]
Wojtowicz-Praga, S.; Torri, J.; Johnson, M.; Steen, V.; Marshall, J.; Ness, E.; Dickson, R.; Sale, M.; Rasmussen, H.S.; Chiodo, T.A.; Hawkins, M.J. Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer. J. Clin. Oncol., 1998, 16(6), 2150-2156.
[http://dx.doi.org/10.1200/JCO.1998.16.6.2150] [PMID: 9626215]
[15]
Skiles, J.W.; Gonnella, N.C.; Jeng, A.Y. The design, structure, and clinical update of small molecular weight matrix metalloproteinase inhibitors. Curr. Med. Chem., 2004, 11(22), 2911-2977.
[http://dx.doi.org/10.2174/0929867043364018] [PMID: 15544483]
[16]
Stickens, D.; Behonick, D.J.; Ortega, N.; Heyer, B.; Hartenstein, B.; Yu, Y.; Fosang, A.J.; Schorpp-Kistner, M.; Angel, P.; Werb, Z. Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development, 2004, 131(23), 5883-5895.
[http://dx.doi.org/10.1242/dev.01461] [PMID: 15539485]
[17]
Ji, J.B.; Li, X.F.; Liu, L.; Wang, G.Z.; Yan, X.F. Effect of low intensity pulsed ultrasound on expression of TIMP-2 in serum and expression of mmp-13 in articular cartilage of rabbits with knee osteoarthritis. Asian Pac. J. Trop. Med., 2015, 8(12), 1043-1048.
[http://dx.doi.org/10.1016/j.apjtm.2015.11.003] [PMID: 26706677]
[18]
Little, C.B.; Barai, A.; Burkhardt, D.; Smith, S.M.; Fosang, A.J.; Werb, Z.; Shah, M.; Thompson, E.W. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum., 2009, 60(12), 3723-3733.
[http://dx.doi.org/10.1002/art.25002] [PMID: 19950295]
[19]
Johnson, A.R.; Pavlovsky, A.G.; Ortwine, D.F.; Prior, F.; Man, C.F.; Bornemeier, D.A.; Banotai, C.A.; Mueller, W.T.; McConnell, P.; Yan, C.; Baragi, V.; Lesch, C.; Roark, W.H.; Wilson, M.; Datta, K.; Guzman, R.; Han, H.K.; Dyer, R.D. Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. J. Biol. Chem., 2007, 282(38), 27781-27791.
[http://dx.doi.org/10.1074/jbc.M703286200] [PMID: 17623656]
[20]
Baragi, V.M.; Becher, G.; Bendele, A.M.; Biesinger, R.; Bluhm, H.; Boer, J.; Deng, H.; Dodd, R.; Essers, M.; Feuerstein, T.; Gallagher, B.M., Jr; Gege, C.; Hochgürtel, M.; Hofmann, M.; Jaworski, A.; Jin, L.; Kiely, A.; Korniski, B.; Kroth, H.; Nix, D.; Nolte, B.; Piecha, D.; Powers, T.S.; Richter, F.; Schneider, M.; Steeneck, C.; Sucholeiki, I.; Taveras, A.; Timmermann, A.; Van Veldhuizen, J.; Weik, J.; Wu, X.; Xia, B. A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models. Arthritis Rheum., 2009, 60(7), 2008-2018.
[http://dx.doi.org/10.1002/art.24629] [PMID: 19565489]
[21]
Gomis-Rüth, F.X. Catalytic domain architecture of metzincin metalloproteases. J. Biol. Chem., 2009, 284(23), 15353-15357.
[http://dx.doi.org/10.1074/jbc.R800069200] [PMID: 19201757]
[22]
Fanjul-Fernández, M.; Folgueras, A.R.; Cabrera, S.; López-Otín, C. Matrix metalloproteinases: evolution, gene regulation and functional analysis in mouse models. Biochim. Biophys. Acta, 2010, 1803(1), 3-19.
[http://dx.doi.org/10.1016/j.bbamcr.2009.07.004] [PMID: 19631700]
[23]
Puente, X.S.; Sánchez, L.M.; Overall, C.M.; López-Otín, C. Human and mouse proteases: a comparative genomic approach. Nat. Rev. Genet., 2003, 4(7), 544-558.
[http://dx.doi.org/10.1038/nrg1111] [PMID: 12838346]
[24]
Vandenbroucke, R.E.; Libert, C. Is there new hope for therapeutic matrix metalloproteinase inhibition? Nat. Rev. Drug Discov., 2014, 13(12), 904-927.
[http://dx.doi.org/10.1038/nrd4390] [PMID: 25376097]
[25]
Tester, A.M.; Cox, J.H.; Connor, A.R.; Starr, A.E.; Dean, R.A.; Puente, X.S.; López-Otín, C.; Overall, C.M. LPS responsiveness and neutrophil chemotaxis in vivo require PMN MMP-8 activity. PLoS One, 2007, 2(3)e312
[http://dx.doi.org/10.1371/journal.pone.0000312] [PMID: 17375198]
[26]
Gearing, A.J.H.; Beckett, P.; Christodoulou, M.; Churchill, M.; Clements, J.; Davidson, A.H.; Drummond, A.H.; Galloway, W.A.; Gilbert, R.; Gordon, J.L. Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature, 1994, 370(6490), 555-557.
[http://dx.doi.org/10.1038/370555a0] [PMID: 8052310]
[27]
Boire, A.; Covic, L.; Agarwal, A.; Jacques, S.; Sherifi, S.; Kuliopulos, A. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell, 2005, 120(3), 303-313.
[http://dx.doi.org/10.1016/j.cell.2004.12.018] [PMID: 15707890]
[28]
Barksby, H.E.; Milner, J.M.; Patterson, A.M.; Peake, N.J.; Hui, W.; Robson, T.; Lakey, R.; Middleton, J.; Cawston, T.E.; Richards, C.D.; Rowan, A.D. Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase activation: implications for cartilage degradation in arthritis. Arthritis Rheum., 2006, 54(10), 3244-3253.
[http://dx.doi.org/10.1002/art.22167] [PMID: 17009259]
[29]
Geurts, N.; Martens, E.; Van Aelst, I.; Proost, P.; Opdenakker, G.; Van den Steen, P.E. Beta-hematin interaction with the hemopexin domain of gelatinase B/MMP-9 provokes autocatalytic processing of the propeptide, thereby priming activation by MMP-3. Biochemistry, 2008, 47(8), 2689-2699.
[http://dx.doi.org/10.1021/bi702260q] [PMID: 18237197]
[30]
Shapiro, S.D.; Kobayashi, D.K.; Ley, T.J. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J. Biol. Chem., 1993, 268(32), 23824-23829.
[PMID: 8226919]
[31]
Hou, P.; Troen, T.; Ovejero, M.C.; Kirkegaard, T.; Andersen, T.L.; Byrjalsen, I.; Ferreras, M.; Sato, T.; Shapiro, S.D.; Foged, N.T.; Delaissé, J.M. Matrix metalloproteinase-12 (MMP-12) in osteoclasts: new lesson on the involvement of MMPs in bone resorption. Bone, 2004, 34(1), 37-47.
[http://dx.doi.org/10.1016/j.bone.2003.08.011] [PMID: 14751561]
[32]
Overall, C.M. Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites. Mol. Biotechnol., 2002, 22(1), 51-86.
[http://dx.doi.org/10.1385/MB:22:1:051] [PMID: 12353914]
[33]
Stracke, J.O.; Hutton, M.; Stewart, M.; Pendás, A.M.; Smith, B.; López-Otin, C.; Murphy, G.; Knäuper, V. Biochemical characterization of the catalytic domain of human matrix metalloproteinase 19. Evidence for a role as a potent basement membrane degrading enzyme. J. Biol. Chem., 2000, 275(20), 14809-14816.
[http://dx.doi.org/10.1074/jbc.275.20.14809] [PMID: 10809722]
[34]
Lu, Y.; Papagerakis, P.; Yamakoshi, Y.; Hu, J.C.; Bartlett, J.D.; Simmer, J.P. Functions of KLK4 and MMP-20 in dental enamel formation. Biol. Chem., 2008, 389(6), 695-700.
[http://dx.doi.org/10.1515/BC.2008.080] [PMID: 18627287]
[35]
Bar-Or, A.; Nuttall, R.K.; Duddy, M.; Alter, A.; Kim, H.J.; Ifergan, I.; Pennington, C.J.; Bourgoin, P.; Edwards, D.R.; Yong, V.W. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis. Brain, 2003, 126(Pt 12), 2738-2749.
[http://dx.doi.org/10.1093/brain/awg285] [PMID: 14506071]
[36]
Uría, J.A.; López-Otín, C. Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity. Cancer Res., 2000, 60(17), 4745-4751.
[PMID: 10987280]
[37]
Xie, X.W.; Wan, R.Z.; Liu, Z.P. Recent research advances in selective matrix metalloproteinase-13 inhibitors as anti-osteoarthritis agents. Chem.Med.Chem, 2017, 12(15), 1157-1168.
[http://dx.doi.org/10.1002/cmdc.201700349] [PMID: 28722301]
[38]
Wang, W.S.; Chen, P.M.; Wang, H.S.; Liang, W.Y.; Su, Y. Matrix metalloproteinase-7 increases resistance to Fas-mediated apoptosis and is a poor prognostic factor of patients with colorectal carcinoma. Carcinogenesis, 2006, 27(5), 1113-1120.
[http://dx.doi.org/10.1093/carcin/bgi351] [PMID: 16474169]
[39]
McGuire, J.K.; Li, Q.; Parks, W.C. Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am. J. Pathol., 2003, 162(6), 1831-1843.
[http://dx.doi.org/10.1016/S0002-9440(10)64318-0] [PMID: 12759241]
[40]
Li, Q.; Park, P.W.; Wilson, C.L.; Parks, W.C. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell, 2002, 111(5), 635-646.
[http://dx.doi.org/10.1016/S0092-8674(02)01079-6] [PMID: 12464176]
[41]
Zhao, Y.G.; Xiao, A.Z.; Park, H.I.; Newcomer, R.G.; Yan, M.; Man, Y.G.; Heffelfinger, S.C.; Sang, Q.X. Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion. Cancer Res., 2004, 64(2), 590-598.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-1932] [PMID: 14744773]
[42]
Yu, Q.; Stamenkovic, I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev., 2000, 14(2), 163-176.
[PMID: 10652271]
[43]
McQuibban, G.A.; Gong, J.H.; Wong, J.P.; Wallace, J.L.; Clark-Lewis, I.; Overall, C.M. Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood, 2002, 100(4), 1160-1167.
[http://dx.doi.org/10.1182/blood.V100.4.1160.h81602001160_1160_1167] [PMID: 12149192]
[44]
Sohail, A.; Sun, Q.; Zhao, H.; Bernardo, M.M.; Cho, J.A.; Fridman, R. MT4-(MMP17) and MT6-MMP (MMP25), A unique set of membrane-anchored matrix metalloproteinases: properties and expression in cancer. Cancer Metastasis Rev., 2008, 27(2), 289-302.
[http://dx.doi.org/10.1007/s10555-008-9129-8] [PMID: 18286233]
[45]
Zucker, S.; Pei, D.; Cao, J.; Lopez-Otin, C. Membrane type-matrix metalloproteinases (MT-MMP). Curr. Top. Dev. Biol., 2003, 54, 1-74.
[http://dx.doi.org/10.1016/S0070-2153(03)54004-2] [PMID: 12696745]
[46]
Li, J.J.; Johnson, A.R. Selective MMP13 inhibitors. Med. Res. Rev., 2011, 31(6), 863-894.
[http://dx.doi.org/10.1002/med.20204] [PMID: 20196103]
[47]
Lovejoy, B.; Welch, A.R.; Carr, S.; Luong, C.; Broka, C.; Hendricks, R.T.; Campbell, J.A.; Walker, K.A.; Martin, R.; Van Wart, H.; Browner, M.F. Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors. Nat. Struct. Biol., 1999, 6(3), 217-221.
[http://dx.doi.org/10.1038/6657] [PMID: 10074939]
[48]
Dormán, G.; Cseh, S.; Hajdú, I.; Barna, L.; Kónya, D.; Kupai, K.; Kovács, L.; Ferdinandy, P. Matrix metalloproteinase inhibitors: a critical appraisal of design principles and proposed therapeutic utility. Drugs, 2010, 70(8), 949-964.
[http://dx.doi.org/10.2165/11318390-000000000-00000] [PMID: 20481653]
[49]
Ruminski, P.G.; Massa, M.; Strohbach, J.; Hanau, C.E.; Schmidt, M.; Scholten, J.A.; Fletcher, T.R.; Hamper, B.C.; Carroll, J.N.; Shieh, H.S.; Caspers, N.; Collins, B.; Grapperhaus, M.; Palmquist, K.E.; Collins, J.; Baldus, J.E.; Hitchcock, J.; Kleine, H.P.; Rogers, M.D.; McDonald, J.; Munie, G.E.; Messing, D.M.; Portolan, S.; Whiteley, L.O.; Sunyer, T.; Schnute, M.E. Discovery of N-(4-Fluoro-3-methoxybenzyl)-6-(2-(((2S,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)-2H-tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A highly selective and orally bioavailable matrix metalloproteinase-13 inhibitor for the potential treatment of osteoarthritis. J. Med. Chem., 2016, 59(1), 313-327.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01434] [PMID: 26653735]
[50]
Devel, L.; Czarny, B.; Beau, F.; Georgiadis, D.; Stura, E.; Dive, V. Third generation of matrix metalloprotease inhibitors: Gain in selectivity by targeting the depth of the S1′ cavity. Biochimie, 2010, 92(11), 1501-1508.
[http://dx.doi.org/10.1016/j.biochi.2010.07.017] [PMID: 20696203]
[51]
Di Pizio, A.; Agamennone, M.; Tortorella, P. Non-zinc-binding inhibitors of MMP-13: GRID-based approaches to rationalize the binding process. Curr. Top. Med. Chem., 2016, 16(4), 449-459.
[http://dx.doi.org/10.2174/1568026615666150813150631] [PMID: 26268339]
[52]
Lanz, J.; Riedl, R. Merging allosteric and active site binding motifs: de novo generation of target selectivity and potency via natural-product-derived fragments. Chem.Med.Chem, 2015, 10(3), 451-454.
[http://dx.doi.org/10.1002/cmdc.201402478] [PMID: 25487909]
[53]
Chen, J.M.; Nelson, F.C.; Levin, J.I.; Mobilio, D.; Moy, F.J.; Nilakantan, R.; Zask, A.; Powers, R. Structure-based design of a novel, potent, and selective inhibitor for MMP-13 utilizing NMR spectroscopy and computer-aided molecular design. J. Am. Chem. Soc., 2000, 122(40), 9648-9654.
[http://dx.doi.org/10.1021/ja001547g]
[54]
Nuti, E.; Casalini, F.; Avramova, S.I.; Santamaria, S.; Cercignani, G.; Marinelli, L.; La Pietra, V.; Novellino, E.; Orlandini, E.; Nencetti, S.; Tuccinardi, T.; Martinelli, A.; Lim, N.H.; Visse, R.; Nagase, H.; Rossello, A. N-O-isopropyl sulfonamido-based hydroxamates: design, synthesis and biological evaluation of selective matrix metalloproteinase-13 inhibitors as potential therapeutic agents for osteoarthritis. J. Med. Chem., 2009, 52(15), 4757-4773.
[http://dx.doi.org/10.1021/jm900261f] [PMID: 19606871]
[55]
Tommasi, R.A.; Weiler, S.; McQuire, L.W.; Rogel, O.; Chambers, M.; Clark, K.; Doughty, J.; Fang, J.; Ganu, V.; Grob, J.; Goldberg, R.; Goldstein, R.; Lavoie, S.; Kulathila, R.; Macchia, W.; Melton, R.; Springer, C.; Walker, M.; Zhang, J.; Zhu, L.; Shultz, M. Potent and selective 2-naphthylsulfonamide substituted hydroxamic acid inhibitors of matrix metalloproteinase-13. Bioorg. Med. Chem. Lett., 2011, 21(21), 6440-6445.
[http://dx.doi.org/10.1016/j.bmcl.2011.08.087] [PMID: 21937229]
[56]
Kolodziej, S.A.; Hockerman, S.L.; DeCrescenzo, G.A.; McDonald, J.J.; Mischke, D.A.; Munie, G.E.; Fletcher, T.R.; Stehle, N.; Swearingen, C.; Becker, D.P. MMP-13 selective isonipecotamide α-sulfone hydroxamates. Bioorg. Med. Chem. Lett., 2010, 20(12), 3561-3564.
[http://dx.doi.org/10.1016/j.bmcl.2010.04.111] [PMID: 20529685]
[57]
Fobian, Y.M.; Freskos, J.N.; Barta, T.E.; Bedell, L.J.; Heintz, R.; Kassab, D.J.; Kiefer, J.R.; Mischke, B.V.; Molyneaux, J.M.; Mullins, P.; Munie, G.E.; Becker, D.P. MMP-13 selective alpha-sulfone hydroxamates: identification of selective P1′ amides. Bioorg. Med. Chem. Lett., 2011, 21(10), 2823-2825.
[http://dx.doi.org/10.1016/j.bmcl.2011.03.095] [PMID: 21493063]
[58]
Whittaker, M.; Floyd, C.D.; Brown, P.; Gearing, A.J. Design and therapeutic application of matrix metalloproteinase inhibitors. Chem. Rev., 1999, 99(9), 2735-2776.
[http://dx.doi.org/10.1021/cr9804543] [PMID: 11749499]
[59]
La Pietra, V.; Marinelli, L.; Cosconati, S.; Di Leva, F.S.; Nuti, E.; Santamaria, S.; Pugliesi, I.; Morelli, M.; Casalini, F.; Rossello, A.; La Motta, C.; Taliani, S.; Visse, R.; Nagase, H.; da Settimo, F.; Novellino, E. Identification of novel molecular scaffolds for the design of MMP-13 inhibitors: a first round of lead optimization. Eur. J. Med. Chem., 2012, 47(1), 143-152.
[http://dx.doi.org/10.1016/j.ejmech.2011.10.035] [PMID: 22088955]
[60]
Li, J.; Rush, T.S., III; Li, W.; DeVincentis, D.; Du, X.; Hu, Y.; Thomason, J.R.; Xiang, J.S.; Skotnicki, J.S.; Tam, S.; Cunningham, K.M.; Chockalingam, P.S.; Morris, E.A.; Levin, J.I. Synthesis and SAR of highly selective MMP-13 inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(22), 4961-4966.
[http://dx.doi.org/10.1016/j.bmcl.2005.08.001] [PMID: 16153831]
[61]
Hu, Y.; Xiang, J.S.; DiGrandi, M.J.; Du, X.; Ipek, M.; Laakso, L.M.; Li, J.; Li, W.; Rush, T.S.; Schmid, J.; Skotnicki, J.S.; Tam, S.; Thomason, J.R.; Wang, Q.; Levin, J.I. Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Bioorg. Med. Chem., 2005, 13(24), 6629-6644.
[http://dx.doi.org/10.1016/j.bmc.2005.07.076] [PMID: 16216515]
[62]
Li, W.; Hu, Y.; Li, J.; Thomason, J.R.; DeVincentis, D.; Du, X.; Wu, J.; Hotchandani, R.; Rush, T.S., III; Skotnicki, J.S.; Tam, S.; Chockalingam, P.S.; Morris, E.A.; Levin, J.I. 3,4-Disubstituted benzofuran P1′ MMP-13 inhibitors: optimization of selectivity and reduction of protein binding. Bioorg. Med. Chem. Lett., 2009, 19(16), 4546-4550.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.008] [PMID: 19625186]
[63]
Ghuman, J.; Zunszain, P.A.; Petitpas, I.; Bhattacharya, A.A.; Otagiri, M.; Curry, S. Structural basis of the drug-binding specificity of human serum albumin. J. Mol. Biol., 2005, 353(1), 38-52.
[http://dx.doi.org/10.1016/j.jmb.2005.07.075] [PMID: 16169013]
[64]
Monovich, L.G.; Tommasi, R.A.; Fujimoto, R.A.; Blancuzzi, V.; Clark, K.; Cornell, W.D.; Doti, R.; Doughty, J.; Fang, J.; Farley, D.; Fitt, J.; Ganu, V.; Goldberg, R.; Goldstein, R.; Lavoie, S.; Kulathila, R.; Macchia, W.; Parker, D.T.; Melton, R.; O’Byrne, E.; Pastor, G.; Pellas, T.; Quadros, E.; Reel, N.; Roland, D.M.; Sakane, Y.; Singh, H.; Skiles, J.; Somers, J.; Toscano, K.; Wigg, A.; Zhou, S.; Zhu, L.; Shieh, W.C.; Xue, S.; McQuire, L.W. Discovery of potent, selective, and orally active carboxylic acid based inhibitors of matrix metalloproteinase-13. J. Med. Chem., 2009, 52(11), 3523-3538.
[http://dx.doi.org/10.1021/jm801394m] [PMID: 19422229]
[65]
Duan, J.J.; Lu, Z.; Wasserman, Z.R.; Liu, R.Q.; Covington, M.B.; Decicco, C.P. Non-hydroxamate 5-phenylpyrimidine-2,4,6-trione derivatives as selective inhibitors of tumor necrosis factor-alpha converting enzyme. Bioorg. Med. Chem. Lett., 2005, 15(12), 2970-2973.
[http://dx.doi.org/10.1016/j.bmcl.2005.04.039] [PMID: 15908214]
[66]
Blagg, J.A.; Noe, M.C.; Wolf-Gouveia, L.A.; Reiter, L.A.; Laird, E.R.; Chang, S.P.; Danley, D.E.; Downs, J.T.; Elliott, N.C.; Eskra, J.D.; Griffiths, R.J.; Hardink, J.R.; Haugeto, A.I.; Jones, C.S.; Liras, J.L.; Lopresti-Morrow, L.L.; Mitchell, P.G.; Pandit, J.; Robinson, R.P.; Subramanyam, C.; Vaughn-Bowser, M.L.; Yocum, S.A. Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14. Bioorg. Med. Chem. Lett., 2005, 15(7), 1807-1810.
[http://dx.doi.org/10.1016/j.bmcl.2005.02.038] [PMID: 15780611]
[67]
Reiter, L.A.; Freeman-Cook, K.D.; Jones, C.S.; Martinelli, G.J.; Antipas, A.S.; Berliner, M.A.; Datta, K.; Downs, J.T.; Eskra, J.D.; Forman, M.D.; Greer, E.M.; Guzman, R.; Hardink, J.R.; Janat, F.; Keene, N.F.; Laird, E.R.; Liras, J.L.; Lopresti-Morrow, L.L.; Mitchell, P.G.; Pandit, J.; Robertson, D.; Sperger, D.; Vaughn-Bowser, M.L.; Waller, D.M.; Yocum, S.A. Potent, selective pyrimidinetrione-based inhibitors of MMP-13. Bioorg. Med. Chem. Lett., 2006, 16(22), 5822-5826.
[http://dx.doi.org/10.1016/j.bmcl.2006.08.066] [PMID: 16942871]
[68]
Freeman-Cook, K.D.; Reiter, L.A.; Noe, M.C.; Antipas, A.S.; Danley, D.E.; Datta, K.; Downs, J.T.; Eisenbeis, S.; Eskra, J.D.; Garmene, D.J.; Greer, E.M.; Griffiths, R.J.; Guzman, R.; Hardink, J.R.; Janat, F.; Jones, C.S.; Martinelli, G.J.; Mitchell, P.G.; Laird, E.R.; Liras, J.L.; Lopresti-Morrow, L.L.; Pandit, J.; Reilly, U.D.; Robertson, D.; Vaughn-Bowser, M.L.; Wolf-Gouviea, L.A.; Yocum, S.A. Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13. Bioorg. Med. Chem. Lett., 2007, 17(23), 6529-6534.
[http://dx.doi.org/10.1016/j.bmcl.2007.09.085] [PMID: 17935984]
[69]
Nara, H.; Sato, K.; Kaieda, A.; Oki, H.; Kuno, H.; Santou, T.; Kanzaki, N.; Terauchi, J.; Uchikawa, O.; Kori, M. Design, synthesis, and biological activity of novel, potent, and highly selective fused pyrimidine-2-carboxamide-4-one-based matrix metalloproteinase (MMP)-13 zinc-binding inhibitors. Bioorg. Med. Chem., 2016, 24(23), 6149-6165.
[http://dx.doi.org/10.1016/j.bmc.2016.09.009] [PMID: 27825552]
[70]
Nara, H.; Kaieda, A.; Sato, K.; Naito, T.; Mototani, H.; Oki, H.; Yamamoto, Y.; Kuno, H.; Santou, T.; Kanzaki, N.; Terauchi, J.; Uchikawa, O.; Kori, M. Discovery of novel, highly potent, and selective matrix metalloproteinase (MMP)-13 inhibitors with a 1,2,4-triazol-3-yl moiety as a zinc binding group using a structure-based design approach. J. Med. Chem., 2017, 60(2), 608-626.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01007] [PMID: 27966948]
[71]
Skiles, J.W.; Gonnella, N.C.; Jeng, A.Y. The design, structure, and therapeutic application of matrix metalloproteinase inhibitors. Curr. Med. Chem., 2001, 8(4), 425-474.
[http://dx.doi.org/10.2174/0929867013373417] [PMID: 11172697]
[72]
Wu, J.; Rush, T.S., III; Hotchandani, R.; Du, X.; Geck, M.; Collins, E.; Xu, Z.B.; Skotnicki, J.; Levin, J.I.; Lovering, F.E. Identification of potent and selective MMP-13 inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(18), 4105-4109.
[http://dx.doi.org/10.1016/j.bmcl.2005.06.019] [PMID: 16005220]
[73]
Matter, H.; Schudok, M. Recent advances in the design of matrix metalloprotease inhibitors. Curr. Opin. Drug Discov. Devel., 2004, 7(4), 513-535.
[PMID: 15338961]
[74]
Rao, B.G. Recent developments in the design of specific Matrix Metalloproteinase inhibitors aided by structural and computational studies. Curr. Pharm. Des., 2005, 11(3), 295-322.
[http://dx.doi.org/10.2174/1381612053382115] [PMID: 15723627]
[75]
Fabre, B.; Ramos, A.; de Pascual-Teresa, B. Targeting matrix metalloproteinases: exploring the dynamics of the s1′ pocket in the design of selective, small molecule inhibitors. J. Med. Chem., 2014, 57(24), 10205-10219.
[http://dx.doi.org/10.1021/jm500505f] [PMID: 25265401]
[76]
Pirard, B. Insight into the structural determinants for selective inhibition of matrix metalloproteinases. Drug Discov. Today, 2007, 12(15-16), 640-646.
[http://dx.doi.org/10.1016/j.drudis.2007.06.003] [PMID: 17706545]
[77]
Heim-Riether, A.; Taylor, S.J.; Liang, S.; Gao, D.A.; Xiong, Z.; Michael August, E.; Collins, B.K.; Farmer, B.T., II; Haverty, K.; Hill-Drzewi, M.; Junker, H.D.; Mariana Margarit, S.; Moss, N.; Neumann, T.; Proudfoot, J.R.; Keenan, L.S.; Sekul, R.; Zhang, Q.; Li, J.; Farrow, N.A. Improving potency and selectivity of a new class of non-Zn-chelating MMP-13 inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(18), 5321-5324.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.151] [PMID: 19692239]
[78]
Gao, D.A.; Xiong, Z.; Heim-Riether, A.; Amodeo, L.; August, E.M.; Cao, X.; Ciccarelli, L.; Collins, B.K.; Harrington, K.; Haverty, K.; Hill-Drzewi, M.; Li, X.; Liang, S.; Margarit, S.M.; Moss, N.; Nagaraja, N.; Proudfoot, J.; Roman, R.; Schlyer, S.; Keenan, L.S.; Taylor, S.; Wellenzohn, B.; Wiedenmayer, D.; Li, J.; Farrow, N.A. SAR studies of non-zinc-chelating MMP-13 inhibitors: improving selectivity and metabolic stability. Bioorg. Med. Chem. Lett., 2010, 20(17), 5039-5043.
[http://dx.doi.org/10.1016/j.bmcl.2010.07.036] [PMID: 20675133]
[79]
Eitner, K.; Koch, U. From fragment screening to potent binders: strategies for fragment-to-lead evolution. Mini Rev. Med. Chem., 2009, 9(8), 956-961.
[http://dx.doi.org/10.2174/138955709788681645] [PMID: 19601891]
[80]
Schulz, M.N.; Hubbard, R.E. Recent progress in fragment-based lead discovery. Curr. Opin. Pharmacol., 2009, 9(5), 615-621.
[http://dx.doi.org/10.1016/j.coph.2009.04.009] [PMID: 19477685]
[81]
Taylor, S.J.; Abeywardane, A.; Liang, S.; Muegge, I.; Padyana, A.K.; Xiong, Z.; Hill-Drzewi, M.; Farmer, B.; Li, X.; Collins, B.; Li, J.X.; Heim-Riether, A.; Proudfoot, J.; Zhang, Q.; Goldberg, D.; Zuvela-Jelaska, L.; Zaher, H.; Li, J.; Farrow, N.A. Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13. J. Med. Chem., 2011, 54(23), 8174-8187.
[http://dx.doi.org/10.1021/jm201129m] [PMID: 22017539]
[82]
Engel, C.K.; Pirard, B.; Schimanski, S.; Kirsch, R.; Habermann, J.; Klingler, O.; Schlotte, V.; Weithmann, K.U.; Wendt, K.U. Structural basis for the highly selective inhibition of MMP-13. Chem. Biol., 2005, 12(2), 181-189.
[http://dx.doi.org/10.1016/j.chembiol.2004.11.014] [PMID: 15734645]
[83]
Piecha, D.; Weik, J.; Kheil, H.; Becher, G.; Timmermann, A.; Jaworski, A.; Burger, M.; Hofmann, M.W. Novel selective MMP-13 inhibitors reduce collagen degradation in bovine articular and human osteoarthritis cartilage explants. Inflamm. Res., 2010, 59(5), 379-389.
[http://dx.doi.org/10.1007/s00011-009-0112-9] [PMID: 19902332]
[84]
Gege, C.; Bao, B.; Bluhm, H.; Boer, J.; Gallagher, B.M.; Korniski, B.; Powers, T.S.; Steeneck, C.; Taveras, A.G.; Baragi, V.M. Discovery and evaluation of a non-Zn chelating, selective matrix metalloproteinase 13 (MMP-13) inhibitor for potential intra-articular treatment of osteoarthritis. J. Med. Chem., 2012, 55(2), 709-716.
[http://dx.doi.org/10.1021/jm201152u] [PMID: 22175799]
[85]
Nara, H.; Sato, K.; Naito, T.; Mototani, H.; Oki, H.; Yamamoto, Y.; Kuno, H.; Santou, T.; Kanzaki, N.; Terauchi, J.; Uchikawa, O.; Kori, M. Discovery of novel, highly potent, and selective quinazoline-2-carboxamide-based matrix metalloproteinase (MMP)-13 inhibitors without a zinc binding group using a structure-based design approach. J. Med. Chem., 2014, 57(21), 8886-8902.
[http://dx.doi.org/10.1021/jm500981k] [PMID: 25264600]
[86]
Nara, H.; Sato, K.; Naito, T.; Mototani, H.; Oki, H.; Yamamoto, Y.; Kuno, H.; Santou, T.; Kanzaki, N.; Terauchi, J.; Uchikawa, O.; Kori, M. Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1″ binding site. Bioorg. Med. Chem., 2014, 22(19), 5487-5505.
[http://dx.doi.org/10.1016/j.bmc.2014.07.025] [PMID: 25192810]
[87]
Spicer, T.P.; Jiang, J.; Taylor, A.B.; Choi, J.Y.; Hart, P.J.; Roush, W.R.; Fields, G.B.; Hodder, P.S.; Minond, D. Characterization of selective exosite-binding inhibitors of matrix metalloproteinase 13 that prevent articular cartilage degradation in vitro. J. Med. Chem., 2014, 57(22), 9598-9611.
[http://dx.doi.org/10.1021/jm501284e] [PMID: 25330343]
[88]
Choi, J.Y.; Fuerst, R.; Knapinska, A.M.; Taylor, A.B.; Smith, L.; Cao, X.; Hart, P.J.; Fields, G.B.; Roush, W.R. Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors. J. Med. Chem., 2017, 60(13), 5816-5825.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00514] [PMID: 28653849]
[89]
Fuerst, R.; Yong Choi, J.; Knapinska, A.M.; Smith, L.; Cameron, M.D.; Ruiz, C.; Fields, G.B.; Roush, W.R. Development of matrix metalloproteinase-13 inhibitors - A structure-activity/structure-property relationship study. Bioorg. Med. Chem., 2018, 26(18), 4984-4995.
[http://dx.doi.org/10.1016/j.bmc.2018.08.020] [PMID: 30249495]

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