Publication Information

{'id': 'https://openalex.org/W2124456960', 'doi': 'https://doi.org/10.1074/jbc.m703286200', 'title': 'Discovery and Characterization of a Novel Inhibitor of Matrix Metalloprotease-13 That Reduces Cartilage Damage in Vivo without Joint Fibroplasia Side Effects', 'display_name': 'Discovery and Characterization of a Novel Inhibitor of Matrix Metalloprotease-13 That Reduces Cartilage Damage in Vivo without Joint Fibroplasia Side Effects', 'publication_year': 2007, 'publication_date': '2007-07-11', 'ids': {'openalex': 'https://openalex.org/W2124456960', 'doi': 'https://doi.org/10.1074/jbc.m703286200', 'mag': '2124456960', 'pmid': 'https://pubmed.ncbi.nlm.nih.gov/17623656'}, 'language': 'en', 'primary_location': {'is_oa': True, 'landing_page_url': 'https://doi.org/10.1074/jbc.m703286200', 'pdf_url': 'http://www.jbc.org/article/S0021925820586742/pdf', 'source': {'id': 'https://openalex.org/S140251998', 'display_name': 'Journal of Biological Chemistry', 'issn_l': '0021-9258', 'issn': ['0021-9258', '1067-8816', '1083-351X'], 'is_oa': True, 'is_in_doaj': True, 'is_core': True, 'host_organization': 'https://openalex.org/P4310320990', 'host_organization_name': 'Elsevier BV', 'host_organization_lineage': ['https://openalex.org/P4310320990'], 'host_organization_lineage_names': ['Elsevier BV'], 'type': 'journal'}, 'license': 'cc-by', 'license_id': 'https://openalex.org/licenses/cc-by', 'version': 'publishedVersion', 'is_accepted': True, 'is_published': True}, 'type': 'article', 'type_crossref': 'journal-article', 'indexed_in': ['crossref'], 'open_access': {'is_oa': True, 'oa_status': 'hybrid', 'oa_url': 'http://www.jbc.org/article/S0021925820586742/pdf', 'any_repository_has_fulltext': False}, 'authorships': [{'author_position': 'first', 'author': {'id': 'https://openalex.org/A5103080014', 'display_name': 'Adam R. 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3680, 3707, 3715, 3725, 3742, 3757, 3766, 3785, 3815, 3949, 4113, 4223, 4233, 4252, 4285, 4357, 4365], 'articular': [20, 219, 486, 723, 2932, 2969], 'cartilage.': [21, 220, 2967], 'Excess': [22, 221], 'MMP13': [23, 73, 116, 145, 164, 222, 272, 315, 344, 363, 573, 708, 845, 883, 939, 1263, 1415, 2670, 3091, 3266, 3311, 3476, 3563, 3581, 3659, 4064, 4096, 4160, 4199, 4212, 4222, 4292, 4389, 4452], 'activity': [24, 223, 1199, 1354, 1368, 3487, 3675, 4108], 'causes': [25, 224], 'cartilage': [26, 121, 195, 225, 320, 394, 463, 724, 895, 946, 1189, 2446, 2522, 2674, 2882], 'degradation': [27, 226, 890, 1190, 2561], 'osteoarthritis,': [29, 228], 'making': [30, 229], 'this': [31, 179, 230, 378, 2531, 2709, 3532, 4031], 'an': [33, 113, 232, 312, 1720, 1876, 1987, 2126, 2631, 2669, 2736, 3090, 3505, 3565, 4114, 4139, 4457], 'attractive': [34, 233], 'therapeutic': [35, 234], 'target.': [36, 235], 'However,': [37, 236, 4427], 'clinically': [38, 237], 'tested': [39, 160, 238, 359, 2686, 3101, 3517, 3608, 3814, 4112], 'MMP': [40, 80, 162, 239, 279, 361, 878, 1085, 1156, 1196, 1201, 1308, 3120, 3197, 3272, 3598, 3655, 3667, 3674, 3735, 3817, 4013], 'inhibitors': [41, 74, 165, 240, 273, 364, 1016, 1086, 1157, 1180, 2152, 3483, 3661, 4014, 4074, 4190, 4200, 4213, 4297, 4453], 'have': [42, 71, 157, 241, 270, 356, 4230, 4392], 'been': [43, 242, 885, 998, 3110, 4231], 'associated': [44, 243], 'with': [45, 94, 244, 293, 1014, 1083, 1181, 1435, 1740, 1758, 1810, 1875, 1979, 2162, 2302, 2334, 2460, 2525, 2571, 2587, 2613, 2801, 2849, 2872, 2908, 2948, 3005, 3157, 3293, 3504, 3627, 3639, 3662, 3853, 3903, 4037, 4138, 4225, 4262, 4294], 'painful,': [47, 246, 1005], 'joint-stiffening': [48, 247, 1006], 'musculoskeletal': [49, 136, 248, 335, 953, 971], 'side': [50, 138, 249, 337, 1008, 1074, 1098, 1140, 1194, 3096], 'effect': [51, 250], 'may': [53, 148, 187, 252, 347, 386], 'be': [54, 253, 3500], 'due': [55, 254], 'to': [56, 64, 86, 96, 190, 255, 263, 285, 295, 389, 434, 451, 497, 887, 965, 983, 1079, 1270, 1362, 1391, 1428, 1519, 1598, 1646, 1655, 1805, 1868, 1913, 1924, 2097, 2140, 2173, 2193, 2476, 2551, 2672, 2752, 2836, 2875, 2928, 2953, 3093, 3113, 3261, 3300, 3324, 3365, 3393, 3407, 3499, 3522, 3586, 3793, 3808, 3828, 3893, 3906, 3911, 3933, 3937, 4016, 4030, 4078, 4084, 4133, 4153, 4171, 4187, 4191, 4195, 4273, 4441, 4460], 'their': [57, 256], 'lack': [58, 257, 3588], 'selectivity.': [60, 259], 'In': [61, 260, 839, 1306, 2535, 3605, 3731, 3760, 3835, 3881, 3961, 4056, 4387], 'our': [62, 261, 3479, 4442], 'efforts': [63, 262], 'develop': [65, 264], 'disease-modifying': [67, 266], 'osteoarthritis': [68, 267, 417, 950, 968], 'drug,': [69, 268, 1147], 'we': [70, 111, 269, 310, 1593, 3516, 3529, 3963, 4177, 4391], 'discovered': [72, 271], 'differ': [76, 275], 'greatly': [77, 276], 'from': [78, 277, 416, 431, 448, 962, 980, 1768, 2895, 3421], 'previous': [79, 278], 'inhibitors;': [81, 280], 'they': [82, 91, 100, 281, 290, 299, 1185, 4167], 'do': [83, 282, 4075], 'not': [84, 127, 283, 326, 710, 1077, 3537, 3921, 4076, 4169, 4179], 'bind': [85, 284, 3889, 4077, 4170], 'catalytic': [88, 287, 955, 973, 1264, 4008, 4032, 4080, 4173], 'zinc': [89, 288, 4009, 4033, 4081, 4174, 4188, 4295], 'ion,': [90, 289], 'are': [92, 291, 1076, 1142, 1557, 3739, 4250], 'noncompetitive': [93, 292, 1523, 3844, 3882, 3972, 4059, 4155], 'respect': [95, 294], 'substrate': [97, 296, 1329, 1643, 3624, 3687, 3888, 3919, 4038, 4122], 'binding,': [98, 297], 'and': [99, 125, 153, 183, 186, 298, 324, 352, 382, 385, 469, 504, 588, 722, 848, 1106, 1200, 1227, 1252, 1280, 1295, 1303, 1360, 1394, 1430, 1491, 1530, 1535, 1555, 1562, 1580, 1609, 1614, 1692, 1704, 1737, 1750, 1795, 1808, 1860, 1865, 1881, 1916, 1960, 1993, 2016, 2080, 2100, 2122, 2143, 2176, 2196, 2225, 2264, 2304, 2325, 2422, 2428, 2464, 2488, 2494, 2527, 2558, 2606, 2700, 2704, 2740, 2776, 2799, 2819, 2831, 2864, 2870, 2879, 2889, 2910, 2918, 2963, 2985, 3016, 3049, 3239, 3242, 3291, 3295, 3351, 3402, 3428, 3450, 3453, 3472, 3491, 3558, 3578, 3613, 3648, 3772, 3832, 3851, 3873, 3886, 3891, 3899, 3910, 3929, 3944, 3958, 4003, 4035, 4069, 4102, 4228, 4241, 4247, 4260, 4278, 4364, 4468, 4473, 4527], 'show': [101, 300], 'extreme': [102, 301], 'selectivity': [103, 302, 1202, 3574, 3590, 3656, 3736, 3818], 'for': [104, 303, 1178, 1298, 1443, 1522, 1601, 1657, 1712, 1784, 2215, 2238, 2391, 2457, 2496, 2708, 2738, 2981, 2987, 3172, 3248, 3297, 3328, 3458, 3482, 3580, 3941, 4184, 4255, 4281, 4291], 'inhibiting': [105, 304], 'MMP13.': [106, 305, 3975], 'By': [107, 306], 'structure-based': [108, 307], 'drug': [109, 308, 4443], 'design,': [110, 309], 'generated': [112, 311, 1275], 'orally': [114, 313, 2547, 2570, 2846, 3152], 'active': [115, 314, 4088], 'inhibitor': [117, 316, 879, 1358, 1377, 1382, 1561, 1693, 1780, 2671, 3092, 3267, 3273, 3312, 3349, 3503, 3534, 3599, 3682, 3845, 3885, 3901, 3928, 3973, 4411], 'effectively': [119, 318, 1187], 'reduces': [120, 319], 'damage': [122, 196, 321, 395, 947, 2675], 'vivo': [124, 323, 2677], 'does': [126, 325, 3920], 'induce': [128, 327, 3094], 'joint': [129, 328, 849, 1073, 1139, 2555, 2816, 2887, 2900, 2973, 3095, 3115, 3306], 'fibroplasias': [130, 329], 'rat': [133, 332, 3104], 'model': [134, 333, 2362, 2398, 2691, 3105, 3375], 'syndrome': [137, 336, 954, 972], 'effects.': [139, 338, 1195], 'Thus,': [140, 339, 3820, 4176], 'highly': [141, 340], 'selective': [142, 341, 3560, 3660], 'inhibition': [143, 342, 1452, 1524, 1584, 1603, 1658, 3316, 3329, 3561, 3883, 3946, 4062, 4094, 4158], 'patients': [147, 346, 727], 'overcome': [149, 348], 'major': [151, 350], 'safety': [152, 351], 'efficacy': [154, 353], 'challenges': [155, 354], 'limited': [158, 357], 'previously': [159, 358, 3112, 4289], 'non-selective': [161, 360, 1084, 1155, 3119, 3194, 3271, 3666], 'inhibitors.': [163, 362], 'such': [166, 365, 1100, 4123], 'as': [167, 366, 512, 1101, 1418, 2359, 2884, 3025, 3232, 3601, 3755, 4124, 4238], 'ones': [169, 368], 'described': [170, 369, 4015, 4290, 4396, 4454], 'here': [171, 370, 4455], 'will': [172, 371], 'help': [173, 372], 'further': [174, 373], 'define': [175, 374], 'role': [177, 376], 'arthritis': [182, 381], 'other': [184, 383, 3527, 3800, 4025], 'diseases': [185, 384], 'soon': [188, 387], 'lead': [189, 388], 'drugs': [191, 390, 990], 'safely': [193, 392], 'halt': [194, 393], 'patients.': [198, 397], 'The': [398, 986, 1325, 1350, 1743, 1764, 1815, 1871, 1936, 1965, 2061, 2130, 2212, 2481, 2594, 2618, 2696, 2723, 2783, 2809, 2827, 2934, 2957, 3236, 3440, 3572, 3915, 4276], 'National': [399], 'Institutes': [400], 'Health': [402], 'has': [403, 884, 997, 1149, 3109], 'estimated': [404], 'more': [406, 1590, 4118], 'than': [407, 1322, 3781], '20': [408, 3794], 'million': [409], 'adults': [410], 'United': [413], 'States': [414], 'suffer': [415], '(OA),': [418], '3The': [419], 'abbreviations': [420, 437], 'used': [421, 438, 1297, 1314, 3111, 3406, 3457], 'are:': [422, 439], 'OAosteoarthritisMMPmatrix': [423, 440], 'metalloproteaseMSSmusculoskeletal': [424, 441], 'syndromeCDcatalytic': [425, 442], 'domainFLfull-lengthAUC0–24': [426, 443], 'harea': [427, 444], 'under': [428, 445, 959, 977], 'curve': [430, 447, 961, 979, 1401], 'time': [432, 449, 963, 981], '0': [433, 450, 964, 982], '24': [435, 452, 966, 984, 3031], 'h.3The': [436], 'h.': [453, 967, 985, 1445, 1714, 2782], 'debilitating': [455], 'disease': [456, 2681], 'which': [458, 1636, 3738], 'protective': [460], 'cushion': [461], 'destroyed,': [465], 'resulting': [466, 585], 'pain': [468, 1107], 'reduced': [470, 1389, 1899, 2305, 3354, 3876, 3952], 'mobility.': [471], 'A': [472, 1260, 3178], 'critical': [473], 'step': [474], 'OA': [476, 726, 852, 2693, 3442], 'pathology': [477], 'breakdown': [479], 'cartilage,': [487, 2563], 'collagen.': [490], 'This': [491, 3339], 'triple': [492], 'helical': [493], 'resistant': [496], 'most': [498, 4439], 'proteases': [499, 3542], 'but': [500, 716], 'efficiently': [502], 'recognized': [503], 'degraded': [505], 'by': [506, 1000, 1276, 1333, 1432, 1453, 1502, 1635, 1718, 1732, 1889, 1921, 1934, 2004, 2066, 2106, 2331, 2540, 2630, 3056, 3564, 4006, 4066, 4097, 4161, 4214], 'enzyme,': [509], 'collagenase-3,': [510], 'known': [511, 3600], 'matrix': [513, 951, 969], '(1Massova': [516], 'L.': [517, 661, 758, 860, 899, 1111, 3126], 'Kotra': [518], 'P.': [519, 671, 694, 768, 791, 909, 1036, 1048, 4301], 'Fridman': [520], 'R.': [521, 667, 764, 905, 1109, 1117, 3124, 3132, 3977, 4332, 4340], 'Mobashery': [522], 'S.': [523, 2503, 4299], 'FASEB': [524], 'J.': [525, 544, 566, 602, 624, 647, 673, 679, 682, 697, 744, 770, 776, 779, 794, 813, 865, 911, 917, 920, 1216, 2337, 2366, 3220, 3691, 4320, 4345], '1998;': [526], '12:': [527], '1075-1095Crossref': [528], 'PubMed': [529, 555, 613, 653, 688, 703, 750, 785, 800, 834, 871, 926, 1028, 1067, 1131, 1169, 1222, 1290, 2317, 2385, 2417, 2509, 2656, 3146, 3226, 3697, 4326, 4351, 4382], 'Scopus': [530, 556, 614, 654, 689, 704, 751, 786, 801, 835, 872, 927, 1029, 1068, 1132, 1170, 1223, 1291, 2318, 2345, 2386, 2418, 2510, 2657, 3147, 3227, 3698, 4327, 4352, 4383], '(700)': [531], 'Google': [532, 558, 616, 656, 691, 706, 753, 788, 803, 818, 837, 874, 929, 1031, 1070, 1134, 1172, 1225, 1293, 1517, 2320, 2347, 2388, 2420, 2512, 2659, 3149, 3229, 3337, 3700, 4054, 4329, 4354, 4385], 'Scholar,': [533, 559, 617, 630, 657, 692, 754, 789, 804, 819, 1032, 4330], '2Knäuper': [534], 'V.': [535, 593, 1125, 3140], 'López-Otin': [536, 594], 'C.': [537, 595, 669, 766, 808, 907, 1113, 2640, 3128], 'Smith': [538, 596], 'B.': [539, 597, 810], 'Knight': [540, 598], 'G.': [541, 543, 599, 601, 2370, 4423], 'Murphy': [542, 600], 'Biol.': [545, 567, 603, 625, 2412, 2652, 4322, 4347], 'Chem.': [546, 568, 604, 626, 3222], '1996;': [547, 605, 650, 700, 747, 797, 815], '271:': [548, 606], '1544-1550Abstract': [549, 607], 'Full': [550, 552, 608, 610], 'Text': [551, 553, 609, 611], 'PDF': [554, 612], '(784)': [557, 615], '3Welgus': [560, 618], 'H.G.': [561, 619], 'Kobayashi': [562, 620], 'D.K.': [563, 621], 'Jeffrey': [564, 622], 'J.J.': [565, 623], '1983;': [569, 627], '258:': [570, 628], '14152-14165Google': [571, 629], 'Scholar).': [572, 707, 838, 875, 930, 1071, 1135, 1173, 2321, 2513, 2660, 3150, 3338, 4055], 'hydrolysis': [576, 1330, 1661], 'collagen': [580, 1665, 1683, 2621], 'at': [581, 1315, 1318, 1339, 1347, 1402, 1440, 1461, 1709, 1878, 1884, 1986, 2084, 2103, 2147, 2183, 2275, 2291, 2767, 3073, 3283, 3346, 3431, 3446, 3520, 3678, 3710, 3728, 3752, 3769, 3896], 'unique': [583, 1078, 4211, 4431, 4524], 'site': [584, 4089], '¾-': [587], '¼-length': [589], 'polypeptide': [590], 'products': [591], '(2Knäuper': [592], '4Mitchell': [631], 'P.G.': [632, 729], 'Magna': [633, 730], 'H.A.': [634, 731], 'Reeves': [635, 732], 'L.M.': [636, 733, 1056], 'Lopresti-Morrow': [637, 734], 'L.L.': [638, 735, 3217], 'Yocum': [639, 736], 'S.A.': [640, 737], 'Rosner': [641, 738], 'P.J.': [642, 739], 'Geoghegan': [643, 740], 'K.F.': [644, 741], 'Hambor': [645, 672, 742, 769, 910], 'J.E.': [646, 743], 'Clin.': [648, 683, 698, 745, 780, 795, 866, 921], 'Investig.': [649, 684, 699, 746, 781, 796, 867, 922], '97:': [651, 701, 748, 798], '761-768Crossref': [652, 749], '(827)': [655, 752], '5Billinghurst': [658, 755], 'R.C.': [659, 756, 897], 'Dahlberg': [660, 757, 898], 'Ionescu': [662, 759, 900], 'M.': [663, 760, 901, 1052, 1054, 3649, 4336], 'Reiner': [664, 761, 902], 'A.': [665, 762, 903, 1058, 2341, 3646, 4334, 4374], 'Bourne': [666, 763, 904, 2377], 'Rorabeck': [668, 765, 906], 'Mitchell': [670, 767, 908], 'Diekmann': [674, 771, 912], 'O.': [675, 772, 913], 'Tschesche': [676, 773, 914, 4337], 'H.': [677, 774, 915, 1123, 1214, 2374, 2644, 3138, 3689, 4305, 4338], 'Chen': [678, 775, 916], 'Wart': [680, 777, 918], 'Van': [681, 778, 919], '1997;': [685, 782, 923, 2314, 2414], '99:': [686, 783, 924], '1534-1545Crossref': [687, 784, 925], '(863)': [690, 787, 928], '6Reboul': [693, 790], 'Pelletier': [695, 792], 'J': [696, 793], '2011-2019Crossref': [702, 799], '(425)': [705, 802], 'found': [711, 3492, 3530], 'normal': [713, 2944], 'adult': [714], 'tissues': [715], 'expressed': [718, 1417, 1787], 'joints': [721, 2584, 2603, 2828, 2867, 3244, 3280], '(4Mitchell': [728], '7Wernicke': [805], 'D.': [806, 1050, 4315], 'Seyfert': [807], 'Hinzmann': [809], 'Gromnica-Ihle': [811], 'E.': [812, 1121, 1789, 3136], 'Rheumatol.': [814], '23:': [816], '590-595PubMed': [817], '8Freemont': [820], 'A.J.': [821, 2648], 'Byers': [822], 'R.J.': [823, 1514, 3334], 'Taiwo': [824], 'Y.O.': [825], 'Hoyland': [826], 'J.A.': [827, 3209], 'Ann.': [828, 1059], 'Rheum.': [829, 1127, 3142], 'Dis.': [830], '1999;': [831, 1064, 2653], '58:': [832], '357-365Crossref': [833], '(64)': [836], 'addition,': [840, 3606, 3962], 'regulated': [841], 'expression': [842, 1282, 1425, 1918], 'human': [844, 893, 1138, 1262, 1414, 2355, 3489, 3611], 'hyaline': [847], 'cartilages': [850], 'induces': [851], 'genetically': [854], 'modified': [855, 2390], 'mice': [856], '(9Neuhold': [857], 'L.A.': [858], 'Killar': [859], 'Zhao': [861], 'W.': [862, 2311, 4342], 'Sung': [863], 'M': [864, 2466], '2001;': [868, 4348], '107:': [869], '35-44Crossref': [870], '(440)': [873], 'Furthermore,': [876, 4110], 'preferentially': [881], 'inhibits': [882], 'shown': [886], 'block': [888], 'explanted': [892], 'osteoarthritic': [894], '(5Billinghurst': [896], 'Based': [931], 'on': [932, 1342, 2283, 2912, 3069, 3798, 4409], 'these': [933, 1015, 3539, 3642, 3708, 3726, 4073, 4162, 4198, 4210], 'findings,': [934], 'it': [935, 1434, 2007, 2068, 3790, 3986, 4428], 'likely': [937], 'direct': [942], 'cause': [943], 'irreversible': [945], 'OA.': [949], 'metalloprotease': [952, 970], 'domain': [956, 974, 1265], 'full-length': [957, 975, 1412], 'area': [958, 976], 'clinical': [987, 1151], 'development': [988], 'inhibit': [992, 1090, 2559, 3538, 4135], 'actions': [994], 'MMPs': [996, 4185], 'plagued': [999], 'association': [1002], 'tendonitis-like': [1007], 'effect,': [1009], 'termed': [1010], '“musculoskeletal': [1011], 'syndrome”': [1012], '(MSS),': [1013], '(10Clark': [1017, 1158], 'I.M.': [1018, 1159], 'Parker': [1019, 1160], 'A.E.': [1020, 1161], 'Expert': [1021, 1162], 'Opin.': [1022, 1163, 4047], 'Ther.': [1023, 1164], 'Targets.': [1024, 1165], '2003;': [1025, 1128, 1166, 3143, 4051], '7:': [1026, 1167], '19-34Crossref': [1027, 1168], '(75)': [1030, 1171], '11Drummond': [1033], 'A.H.': [1034, 1042], 'Beckett': [1035], 'Brown': [1037], 'P.D.': [1038], 'Bone': [1039], 'E.A.': [1040], 'Davidson': [1041], 'Galloway': [1043], 'W.A.': [1044], 'Gearing': [1045], 'A.J.H.': [1046], 'Huxley': [1047], 'Laber': [1049], 'McCourt': [1051], 'Whittaker': [1053], 'Wood': [1055], 'Wright': [1057], 'N.': [1060], 'Y.': [1061], 'Acad.': [1062], 'Sci.': [1063], '878:': [1065], '228-235Crossref': [1066], '(198)': [1069], 'Such': [1072], 'effects': [1075, 1099, 1141], 'humans.': [1080], 'Rats': [1081], 'dosed': [1082, 2548, 2569, 2845, 3153], '(i.e.': [1087, 3167], 'compounds': [1088, 1254], 'several': [1091, 2253, 2395], 'or': [1092, 2474, 2573, 2855, 3159, 3270, 3603, 3994, 4024, 4083], 'all': [1093, 4012], 'MMPs)': [1094], 'also': [1095, 1594, 3969], 'display': [1096], 'MSS-like': [1097, 1193], 'soft': [1102], 'tissue': [1103, 2557], 'fibroplasias,': [1104], 'inflammation,': [1105], '(12Renkiewicz': [1108, 3123], 'Qiu': [1110, 3125], 'Lesch': [1112, 3127], 'Sun': [1114, 3129], 'X.': [1115, 3130], 'Devalaraja': [1116, 3131], 'Cody': [1118, 3133], 'T.': [1119, 3134], 'Kaldjian': [1120, 3135], 'Welgus': [1122, 3137], 'Baragi': [1124, 3139], 'Arthritis': [1126, 3141], '48:': [1129, 3144], '1742-1749Crossref': [1130, 3145], '(167)': [1133, 3148], 'Although': [1136], 'reversible': [1143, 4104], 'upon': [1144], 'withdrawal': [1145], 'MSS': [1148, 3107], 'halted': [1150], 'trials': [1152], 'many': [1154], 'We': [1174, 3151, 4091, 4446], 'began': [1175], 'search': [1177, 2361], 'MMP13-selective': [1179], 'hypothesis': [1183], 'would': [1186], 'prevent': [1188, 2673, 4274], 'without': [1191], 'causing': [1192], 'Activity': [1197], 'Assays-MMP13': [1198], 'assays': [1203, 1310, 3618, 3709, 3727], 'employed': [1204], 'thioester': [1206, 1486], 'substrate,': [1207, 1248, 1487, 1563], 'acetyl-Pro-Leu-Gly-[2-mercapto-4-methyl-pentanoyl]-Leu-Gly-O-ethyl': [1208], 'ester': [1209], '(Bachem': [1210], 'Corp.': [1211], '#H-7145)': [1212], '(13Weingarten': [1213, 3688], 'Feder': [1215, 3690], 'Anal.': [1217, 2504, 3692], 'Biochem.': [1218, 2505, 3693, 4375], '1985;': [1219, 3694], '147:': [1220, 3695], '437-440Crossref': [1221, 3696], '(90)': [1224, 3699], 'Scholar)': [1226, 1518, 2348, 2421], 'reaction': [1228, 1465], 'mixtures': [1229, 1466, 1654], 'containing': [1230, 1467, 2115], '50': [1231, 1468, 1667, 1947, 2022, 2037, 2047, 2070, 2109], 'mm': [1232, 1240, 1243, 1247, 1437, 1469, 1475, 1478, 1481, 1668, 1674, 1677, 1948, 1958, 2023, 2029, 2038, 2044, 2048, 2054, 2071, 2110, 2117, 2120], 'N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic': [1233], 'acid': [1234, 2170, 3196, 3496], '(Hepes)': [1235], 'buffer': [1236, 1471, 1670, 1950, 2025, 2040, 2050, 2073, 2112, 2233, 2249, 3768, 3789, 3830], '(pH': [1237, 1472, 1671, 1951, 2026, 2041, 2051, 2074, 2113, 2234, 2250], '7.0),': [1238, 1473, 2235], '10': [1239, 1474, 1673, 1957, 2028, 2043, 2053, 2116, 2477], 'CaCl2,': [1241, 1476, 1675, 2118], '1': [1242, 1436, 1444, 1480, 2181, 2217, 2839, 3494, 3519, 3549, 3577, 3840, 3858, 3871, 4068, 4129, 4227, 4259], '5,5′-dithiobis(2-nitrobenzoic': [1244, 1482], 'acid),': [1245, 1483], '0.1': [1246, 2119, 2174, 2230, 2246], '0.005%': [1249, 1488, 1689], 'Brij': [1250, 1489, 1690], '35,': [1251, 1490, 1691], 'test': [1253, 3404], 'dissolved': [1255, 2065], 'Me2SO': [1257, 1695, 2154], '(1%': [1258, 1696], 'final).': [1259, 1697, 2168], 'recombinant': [1261], '(CD)': [1266], 'construct': [1267, 4192], 'encompassing': [1268], 'Tyr-104': [1269], 'Asp-270': [1271], '(SWISS-PROT': [1272], 'P45452)': [1273], 'was': [1274, 1296, 1313, 1331, 1355, 1416, 1459, 1702, 1766, 1786, 1866, 1873, 1882, 1898, 1911, 1919, 2002, 2064, 2095, 2101, 2133, 2171, 2191, 2484, 2492, 2523, 2533, 2610, 2628, 2685, 2817, 2825, 2901, 2916, 2936, 2974, 3062, 3100, 3384, 3390, 3405, 3625, 3676, 3705, 3723, 3791], 'synthetic': [1277], 'gene': [1278], 'methods': [1279], 'bacterial': [1281], '(14Biochem.': [1283], 'Biophys.': [1284, 4376], 'Res.': [1285, 2381, 4377], 'Commun.': [1286, 4378], '1992;': [1287], '186:': [1288], '143-149Crossref': [1289], '(34)': [1292], 'Scholar),': [1294, 1542, 1621, 2389, 3230, 4355], 'both': [1299, 3640], 'high': [1300, 3573], 'throughput': [1301], 'screening': [1302], 'crystallographic': [1304, 4474], 'studies.': [1305], 'IC50': [1309, 1379, 1765, 3506, 3635, 4140], 'enzyme': [1312, 3895, 3909], 'level': [1317, 3436], 'least': [1319, 1505, 3447, 3679], '10-fold': [1320], 'lower': [1321], 'IC50.': [1324], 'initial': [1326, 1568, 2327, 3319], 'rate': [1327, 1386, 1996, 2769, 3320, 3344, 3939], 'determined': [1332, 3964, 4204], 'monitoring': [1334], 'increase': [1336], 'absorbance': [1338], '412': [1340], 'nm': [1341, 3511, 4145], 'microplate': [1344], 'reader': [1345], 'thermostatted': [1346, 1804], '25': [1348, 1462, 3637], '°C.': [1349, 2149, 2185], '%': [1351, 1365, 1773], 'control': [1353, 1367, 1775, 3422], 'plotted': [1356], 'against': [1357, 1779, 3525, 3609], 'concentration': [1359, 1383, 3813], 'fit': [1361, 1501, 1595, 3323, 3361, 3934], 'equation': [1364, 1521, 1600], '=': [1369, 1544, 1623, 3434, 3507, 3555, 3855, 3861, 3868, 4141, 4514], '100/(1': [1370], '+': [1371, 1547, 1549, 1551, 1625, 1627], '([I]/IC)slope50),': [1372], 'where': [1373, 1384, 1553, 1630, 3619, 4197, 4518], '[I]': [1374, 1554], 'concentration,': [1378], '50%': [1388], 'relative': [1390, 2760], 'control,': [1393], 'slope': [1395, 1398], 'its': [1403, 4131], 'inflection': [1404], 'point.': [1405], 'Steady-state': [1406, 1497, 1536, 1615], 'Kinetics': [1407], 'Inhibition': [1409, 3672], 'MMP13-Recombinant': [1411], '(FL)': [1413], 'latent': [1420], 'proenzyme': [1421], 'baculovirus': [1424], 'system,': [1426], 'purified': [1427], 'homogeneity,': [1429], 'activated': [1431, 2591], 'incubating': [1433], 'p-aminophenylmercuric': [1438], 'acetate': [1439], '37': [1441, 1914], '°C': [1442, 1463, 1711, 1807, 2105], 'To': [1446, 1586, 3085], 'determine': [1447, 3086], 'kinetic': [1449, 3313, 3367], 'mechanism': [1450, 3314, 4060, 4156], 'Compound': [1454, 1495, 2216, 2239, 2479, 2549, 2577, 2683, 2853, 3098, 3163, 3199, 3268, 3274, 3493, 3518, 3568, 3592, 3632, 3669, 3702, 3720, 3747, 3775, 3796, 3824, 3839, 3966, 4098, 4128], '1,': [1455, 3797, 3849], 'MMP13FL': [1456, 1699, 2592, 3847], '(5': [1457], 'nm)': [1458, 1701, 3557], 'assayed': [1460, 3677], 'Hepes': [1470, 2232, 2248, 3745], '140': [1477], 'NaCl,': [1479, 1678], '0–200': [1484], 'μm': [1485, 2478, 3524, 3638], 'various': [1492, 2574, 3326, 3348, 4388], 'concentrations': [1493, 1559, 3350], '1.': [1496, 3759], 'kinetics': [1498, 3837], 'data': [1499, 1597, 2272, 3321, 3345, 3364, 3459, 3936, 4183, 4245], 'were': [1500, 1707, 1716, 1730, 1748, 1798, 1932, 1941, 1967, 2155, 2179, 2204, 2256, 2273, 2300, 2329, 2431, 2455, 2568, 2585, 2596, 2604, 2713, 2728, 2749, 2785, 2829, 2834, 2844, 2862, 2868, 2995, 3023, 3044, 3051, 3245, 3281, 3322, 3417, 3426], 'global': [1503], 'non-linear': [1504], 'squares': [1506], 'regression': [1507], 'using': [1508, 1752, 1900, 2125, 2278, 2306, 2349, 2400, 2433, 2977, 2997, 3035, 3040, 3064, 3330, 3684, 4105, 4116, 4216], 'GraFit': [1509, 3331], 'Version': [1510, 1761, 3037], '5': [1511], 'software': [1512, 3039, 3332, 3378], '(15Leatherbarrow': [1513, 3333], 'GraFit.': [1515, 3335], '2005;': [1516, 3336], '(16Segel': [1525, 1604], 'I.H.': [1526, 1605], 'Enzyme': [1527, 1537, 1606, 1616], 'Kinetics:': [1528, 1607], 'Behavior': [1529, 1608], 'Analysis': [1531, 1610], 'Rapid': [1533, 1612], 'Equilibrium': [1534, 1613], 'Systems.': [1538, 1617], '1975;': [1539, 1618], ':': [1540, 1619], '125Google': [1541, 1620], '1/v': [1543, 1622], '[(Km/': [1545], 'Vmax)(1': [1546], '([I]/Ki))(1/[S])]': [1548, 1626], '[(1/Vmax)(1': [1550, 1628], '([I]/Ki))],': [1552], '[S]': [1556], 'respectively,': [1564], 'v': [1565], 'velocity,': [1569], 'Km': [1570, 3867], 'Michaelis': [1573], 'constant,': [1574], 'Vmax': [1575, 3860], 'maximal': [1578], 'rate,': [1579], 'Ki': [1581, 1638, 3854], 'constant.': [1585], 'rule': [1587], 'out': [1588, 3392, 3430, 3741, 3765], 'elaborate': [1591], 'model,': [1592, 2682], 'mixed': [1602, 2156], '[(Km/Vmax)(1': [1624], '+([I]/αKi))],': [1629], 'α': [1631], 'factor': [1634], 'changed': [1640], 'when': [1641, 3515, 3607, 4111], 'bound': [1645, 3918, 4186], 'enzyme.': [1648, 2593], 'Type': [1649, 1975], 'Collagen': [1651], 'Cleavage': [1652], 'Assay-Reaction': [1653], 'assay': [1656, 2634, 4115], 'MMP13-catalyzed': [1660, 4136], 'contained': [1666, 1819, 2218, 2241], 'Tris-HCl': [1669, 1949], '7.4),': [1672], '150': [1676], '0.5': [1679, 1980, 2207], 'mg/ml': [1680, 2099], 'soluble': [1681, 2093, 2189, 3792], 'bovine': [1682], '(Elastin': [1684], 'Products': [1685], 'Co.': [1686], '#': [1687], 'CJ385),': [1688], 'Activated': [1698], '(2': [1700, 2059], 'added,': [1703], 'reactions': [1706], 'incubated': [1708, 2180], '23': [1710], '18': [1713], 'Reactions': [1715], 'stopped': [1717], 'adding': [1719, 1922], 'equal': [1721, 3454, 3904], 'volume': [1722], '2×': [1724], 'SDS': [1725], 'sample': [1726, 2532], 'loading': [1727], 'buffer.': [1728], 'Proteins': [1729], 'separated': [1731], 'denaturing': [1733], 'electrophoresis': [1734], '(8%': [1735], 'Trisglycine)': [1736], 'then': [1738, 2937, 2946, 2975], 'visualized': [1739], 'Coomassie': [1741], 'R-250.': [1742], '¾-length': [1744, 1776], 'product': [1745, 1777], 'bands': [1747], 'scanned': [1749], 'quantified': [1751, 2629, 3626], 'Bio-Rad': [1754], 'GS-700': [1755], 'imaging': [1756], 'densitometer': [1757], 'Quantity': [1759], 'One': [1760], '4.0': [1762], 'software.': [1763], 'defined': [1767], 'plot': [1770], 'density': [1778], 'concentration.': [1781], 'Crystallography-MMP13CD': [1782], 'crystallography': [1785, 4215], 'coli': [1790], 'BL21(DE3)': [1791], 'cells': [1792, 1931, 1938, 1966], 'harboring': [1793], 'pLysS': [1794], 'pGEMEX-1/MMP13CD.': [1796], 'Cells': [1797], 'grown': [1799], '20-liter': [1802], 'fermentor': [1803], '30': [1806, 2850, 3508], 'sparged': [1809], '∼8': [1811], 'liters': [1812, 1945, 1981, 2010], 'air/min.': [1814], 'medium': [1816, 2483, 2491], '(15': [1817], 'liters)': [1818], '260': [1820, 1827, 1834, 1840], 'g': [1821, 1828, 1835, 1841, 1848, 1852, 1855, 1862], 'Difco': [1823, 1837], '0127': [1824], 'yeast': [1825], 'extract,': [1826], 'acidicase': [1830], 'peptone': [1831, 1844], '(BBL': [1832, 1845], '211843),': [1833], '0259': [1838], 'casitone,': [1839], 'gelysate': [1843], '211870),': [1846], '26': [1847, 1851, 1854], 'KH2PO4,': [1850], 'K2HPO4,': [1853], 'Na2HPO4': [1857], '•7': [1858], 'H2O,': [1859], '1.5': [1861], 'ampicillin': [1864], 'titrated': [1867], 'pH': [1869, 1885, 3743, 3770, 3786, 3833], '6.8.': [1870], 'culture': [1872, 1905, 2482], 'stirred': [1874], 'impeller': [1877, 1988], '600': [1879], 'rpm': [1880, 1992], 'maintained': [1883], '6.8': [1886], '±': [1887, 3509, 3857, 3863, 3870, 4143], '0.2': [1888, 2226], 'addition': [1891], '85%': [1893, 2261], 'lactic': [1894], 'acid,': [1895, 4021, 4023, 4269], 'whereas': [1896, 2236, 3784], 'foam': [1897], 'Antifoam': [1901], '289.': [1902], 'At': [1903, 2514], 'A600': [1906], '∼': [1907], '10,': [1908], 'temperature': [1910, 2755], 'raised': [1912], '°C,': [1915], 'induced': [1920, 2690], 'isopropyl-β-d-thiogalactopyranoside': [1923], '3.2': [1925], 'mm.': [1926], 'After': [1927, 2087, 2186, 2252, 2394, 2579, 2886, 3255], '3': [1928, 2450, 2580, 3670, 3782], 'h': [1929, 2182, 2599], 'collected': [1933, 2274, 2495, 3282], 'centrifugation.': [1935], 'wet': [1937], '(400': [1939], 'g)': [1940], 'suspended': [1942], '1.3': [1944], '8.0)': [1952], 'plus': [1953, 2076, 4267], '1%': [1954, 2031], 'Triton': [1955, 2032], 'X-100,': [1956], 'MgCl2,': [1959], '40': [1961], 'μl': [1962, 2615], 'Benzonase.': [1964], 'twice': [1968, 2486, 2612, 2847], 'passed': [1969, 2134], 'through': [1970, 2135], 'Dyno-Mill': [1972], '(Glenn': [1973], 'Mills': [1974], 'KDL': [1976], '0.6-liter': [1977], 'chamber)': [1978], '0.25–0.50-mm': [1983], 'glass': [1984], 'beads': [1985], 'speed': [1989], '4200': [1991], 'flow': [1995], '100': [1998, 2276, 3523, 3753, 3809], 'ml/min.': [1999], 'Insoluble': [2000], 'material': [2001], 'washed': [2003, 2019], 'sequentially': [2005], 'suspending': [2006, 2067], '2': [2009, 2240, 2458, 2550, 2598, 2684, 2854, 3099, 3164, 3176, 3269, 3510, 3569, 3579, 3633, 3703, 3721, 3748, 3776, 3825, 3864, 3967, 4070, 4099, 4229, 4254, 4261], 'each': [2011], 'following': [2014], 'solutions': [2015, 2178], 'centrifuging': [2017], 'mixtures:': [2020], '1)': [2021], 'glycine': [2024, 2039], '10.0),': [2027, 2042], 'EDTA,': [2030], 'X-100': [2033], '(3': [2034], 'times);': [2035], '2)': [2036], 'EDTA;': [2045], '3)': [2046], 'Tris·HCl': [2049, 2072, 2111], '8.0),': [2052], 'dithiothreitol;': [2055], '4)': [2056], 'deionized': [2057, 2806], 'water': [2058, 2429], 'times).': [2060], 'pellet': [2063], '7.6)': [2075, 2114], '6': [2077, 3787, 4144], 'm': [2078, 2227, 2231, 2243, 2247], 'guanidine': [2079], 'stirring': [2081], 'solution': [2083, 2203, 2214, 2263, 2324], 'room': [2085, 2772], 'temperature.': [2086], 'centrifugation,': [2088, 2187], 'fraction': [2094], 'brought': [2096], '∼0.15': [2098], 'refolded': [2102, 2131], '–15': [2104], 'diafiltration': [2107], 'into': [2108, 2920], 'ZnCl2,': [2121], '10%': [2123, 3287], 'glycerol': [2124], 'Amicon': [2127], 'S3Y10': [2128], 'membrane.': [2129], '0.2-μm': [2137], 'filter,': [2138], 'concentrated': [2139, 2192], '∼1': [2141], 'mg/ml,': [2142, 2195], 'frozen': [2144], 'aliquots': [2146], '–70': [2148], 'For': [2150, 3369], 'crystallization,': [2151], '5:1': [2159], 'molar': [2160], 'ratio': [2161], 'MMP13CD': [2163, 3490, 4266, 4282], '(1': [2164, 2448], 'mg/ml)': [2165], '(Me2SO,': [2166], '<5%': [2167], 'Acetohydroxamic': [2169], 'added': [2172, 4272], 'm,': [2175], '4': [2184, 3038, 3275], '7–20': [2194], '2–4-μl': [2197], 'hanging': [2198], 'drops': [2199], '1:1': [2201], 'protein:reservoir': [2202], 'equilibrated': [2205], 'over': [2206, 4532], 'ml': [2208], 'reservoir': [2210, 2213], 'solution.': [2211], '18–22%': [2219], 'polyethylene': [2220], 'glycol': [2221], 'monomethyl': [2222], 'ether': [2223], '5000': [2224], 'Li2SO4': [2228], '2.1': [2242], '(NH4)2SO4': [2244], '7.5).': [2251], 'weeks,': [2254], 'crystals': [2255, 4390], 'cryo-preserved': [2257], '15%': [2259], 'glycerol,': [2260], 'well': [2262], 'flash-frozen': [2265], 'stream': [2268], 'nitrogen.': [2270], 'Diffraction': [2271, 4244], 'K': [2277], 'MARCCD-165': [2280], 'detector': [2281], 'installed': [2282], 'Industrial': [2285], 'Macromolecular': [2286], 'Crystallographer': [2287], 'Associations': [2288], 'beamline': [2289], '17-ID': [2290], 'Advanced': [2293], 'Photon': [2294], 'Source': [2295], 'Argonne,': [2297], 'IL.': [2298], 'Data': [2299, 4236], 'integrated': [2301], 'HKL2000': [2303], 'SCALEPACK': [2307], '(17Otwinowski': [2308], 'Z.': [2309, 2368], 'Minor': [2310], 'Methods': [2312], 'Enzymol.': [2313], '276:': [2315], '307-326Crossref': [2316], '(38527)': [2319], 'During': [2322, 3981], 'structure': [2323, 2352, 4182, 4459], 'refinement,': [2326], 'phases': [2328], 'obtained': [2330], 'molecular': [2332], 'replacement': [2333], 'AMoRe': [2335], '(18Navaza': [2336], 'Acta': [2338, 2408], 'Crystallogr.': [2339, 2409, 2413], 'Sect.': [2340, 2410], '1994;': [2342], '50:': [2343], '157-163Crossref': [2344], '(5028)': [2346], 'crystal': [2351, 4181], 'coordinates': [2353, 4220], 'MMP3': [2356], '(PDB': [2357], '1CIZ)': [2358], '(19Berman': [2363], 'H.M.': [2364], 'Westbrook': [2365], 'Feng': [2367], 'Gilliland': [2369], 'Bhat': [2371], 'T.N.': [2372], 'Weissig': [2373], 'Shindyalov': [2375], 'I.N.': [2376], 'P.E.': [2378], 'Nucleic': [2379], 'Acids': [2380], '2000;': [2382, 3223], '28:': [2383], '235-242Crossref': [2384], '(27327)': [2387], 'sequence': [2392], 'differences.': [2393], 'rounds': [2396], 'refinement': [2399, 4248, 4475], 'REFMAC5': [2401], '(20Murshudov': [2402], 'G.N.': [2403], 'Vagin': [2404], 'A.A.': [2405], 'Dodson': [2406], 'E.J.': [2407], 'D': [2411], '53:': [2415], '240-255Crossref': [2416], '(13855)': [2419], 'manual': [2423], 'correction,': [2424], 'inhibitor,': [2426, 3121, 3198, 3668], 'acetohydroxamate,': [2427], 'molecules': [2430], 'placed': [2432], 'QUANTA-2000': [2434], '(Accelrys,': [2435], 'San': [2436, 3381], 'Diego,': [2437], 'CA).': [2438], 'Cytokine-stimulated': [2439], 'Cartilage': [2440, 2537], 'Explant': [2441], 'Degradation': [2442, 2538], 'Assay-': [2443], 'Bovine': [2444], 'nasal': [2445], 'explants': [2447], '×': [2449, 3029], 'mm,': [2451], '9': [2452], 'per': [2453, 2566, 2726, 2774, 3033, 3165], 'group)': [2454, 2567, 2727], 'cultured': [2456], 'weeks': [2459, 2858], 'interleukin-1α': [2461], '(50': [2462, 2467], 'ng/ml)': [2463, 2468], 'oncostatin': [2465], 'presence': [2471, 2878, 3916], 'vehicle': [2473, 2572, 3158], 'up': [2475, 3521, 3807], '2.': [2480, 2578], 'refreshed': [2485], 'weekly,': [2487], 'conditioned': [2490], 'pooled': [2493], 'quantification': [2497], 'hydroxyproline': [2499, 2529], '(21Prockop': [2500], 'D.J.': [2501], 'Udenfriend': [2502], '1960;': [2506], '1:': [2507], '228-239Crossref': [2508], '(724)': [2511], 'end': [2516], 'study,': [2519, 3317], 'remaining': [2521, 2958], 'digested': [2524], 'papain,': [2526], 'measured.': [2534], 'Vivo': [2536], 'Induced': [2539], 'Exogenous': [2541], 'MMP13-To': [2542], 'assess': [2543, 2665, 3301], 'ability': [2545, 2667, 4132], 'reach': [2552], 'knee': [2554, 2583, 2602, 2815, 2866], 'target': [2556], 'MMP13-induced': [2560], 'rats': [2564, 3155, 3182, 3262], '(12': [2565, 2725], 'doses': [2575], 'h,': [2581, 2775], 'injected': [2586], '12': [2588], 'μg': [2589], 'animals': [2595, 2833, 2843, 2861], 'sacrificed': [2597], 'later,': [2600, 2859], 'opened,': [2605], 'synovial': [2608], 'space': [2609, 4419], 'lavaged': [2611], '80': [2614], 'saline.': [2617], 'neoepitope': [2622, 3630], 'biomarker': [2623], 'lavage': [2626], 'fluid': [2627], 'enzyme-linked': [2632], 'immunosorbent': [2633], '(22Otterness': [2635], 'I.G.': [2636], 'Downs': [2637], 'J.T.': [2638], 'Lane': [2639], 'Bliven': [2641], 'M.L.': [2642], 'Stukenbrok': [2643], 'Scampoli': [2645], 'D.N.': [2646], 'Milici': [2647], 'Mézes': [2649], 'P.S.': [2650], '18:': [2654], '331-341Crossref': [2655], '(56)': [2658], 'Surgical': [2661], 'Model': [2662, 3014, 3079], 'OA-To': [2664], 'chronic': [2680], 'surgically': [2689], 'rabbits.': [2695], 'Institutional': [2697], 'Animal': [2698, 2744], 'Care': [2699, 2745], 'Use': [2701], 'Committee': [2702], 'reviewed': [2703], 'approved': [2705], 'protocol': [2707], 'rabbit': [2710, 2791, 3441], 'study.': [2711], 'Animals': [2712], 'male': [2714], 'specific-pathogen-free': [2715], 'New': [2716], 'Zealand': [2717], 'White': [2718], 'rabbits': [2719, 2724, 2784], 'weighing': [2720], '2.5–3.5': [2721], 'kg.': [2722], 'individually': [2729], 'housed': [2730], 'stainless': [2732], 'steel': [2733], 'caging': [2734], 'Association': [2737], 'Assessment': [2739], 'Accreditation': [2741], 'Laboratory': [2743], 'accredited': [2746], 'facility.': [2747], 'Rooms': [2748], 'environmentally': [2750], 'controlled': [2751], 'provide': [2753], '61–71': [2757], '°F,': [2758], 'humidity': [2761], '35–65%,': [2763], '100%': [2764], 'fresh': [2765], 'air': [2766], '10–12': [2771], 'exchanges': [2773], 'light:dark': [2778], 'cycle': [2779], '12:12': [2781], 'fed': [2786], 'designated': [2788], 'amount': [2789], 'chow': [2792], '(LabDiet': [2793], '5321,': [2794], 'PMI': [2795], 'Nutrition,': [2796], 'Brentwood,': [2797], 'MO)': [2798], 'provided': [2800], 'continuous': [2803], 'supply': [2804], 'drinking': [2807], 'water.': [2808], 'anterior': [2810], 'cruciate': [2811], 'ligament': [2812], 'one': [2814, 2986], 'transected,': [2818], '∼70%': [2820], 'medial': [2823], 'meniscus': [2824], 'excised.': [2826], 'closed,': [2830], 'allowed': [2835], 'recover.': [2837], 'Beginning': [2838], 'day': [2840, 3166], 'post-operation,': [2841], 'daily': [2848, 3186], 'mg/kg': [2851, 3161, 3191], 'vehicle.': [2856], 'Five': [2857], 'sacrificed,': [2863], 'removed': [2869], 'stained': [2871], 'India': [2873, 2923], 'ink': [2874, 2924, 2959], 'evaluate': [2876], 'severity': [2880], 'lesions': [2883, 2994, 3050], 'follows.': [2885], 'removal': [2888], 'separation': [2890], 'femoral': [2893, 2983], 'condyle': [2894, 2984], 'tibial': [2897, 2989], 'plateau,': [2898], 'wrapped': [2902], 'paper': [2905, 2951], 'towel': [2906, 2952], 'moistened': [2907], 'saline': [2909, 2945], 'kept': [2911], 'ice.': [2913], 'Each': [2914, 2968], 'bone': [2915, 2935], 'unwrapped': [2917], 'dipped': [2919], 'waterproof': [2921], 'drawing': [2922], '(Sanford': [2925], 'no.': [2926], '4418)': [2927], 'immerse': [2929], 'entire': [2931], 'surface.': [2933], 'briefly': [2938], 'rinsed': [2939], 'beaker': [2942], 'blotted': [2947], 'clean': [2950], 'remove': [2954], 'excess': [2955], 'ink.': [2956], 'reveals': [2960], 'damage,': [2961], 'fibrillation,': [2962], 'fissuring': [2964], 'surface': [2970], 'imaged': [2976], 'three': [2978], 'different': [2979, 3420, 4406], 'angles': [2980], 'plateau.': [2990], 'Images': [2991, 3022, 3043], 'captured': [2996], 'Nikon': [2999], 'SMZ800': [3000], 'dissecting': [3001], 'microscope': [3002, 3072], '(1×': [3003], 'setting)': [3004], 'SPOT': [3007, 3036], 'Insight': [3008], 'color': [3009], 'CCD': [3010], 'camera': [3011], '(Diagnostics': [3012], 'Instruments': [3013], '320)': [3015], 'Cadmet': [3018], 'MS2000': [3019], 'light': [3020, 3298], 'source.': [3021], 'saved': [3024], 'bitmap': [3026], 'files': [3027], '(1600': [3028], '1200,': [3030], 'bits': [3032], 'pixel)': [3034], 'auto-exposure': [3041], 'setting.': [3042], 'burned': [3045], 'onto': [3046], 'compact': [3047], 'discs,': [3048], 'demarcated': [3052], 'blinded': [3054], 'fashion': [3055], 'two': [3057, 3448, 3658], 'independent,': [3058], 'trained': [3059], 'investigators.': [3060], 'Calibration': [3061], 'performed': [3063], 'images': [3065], 'standards': [3067], 'taken': [3068], 'same': [3071, 3075], 'time.': [3076], 'Rat': [3077], 'Fibroplasia': [3078], 'Musculoskeletal': [3081], 'Joint': [3082], 'Side': [3083], 'Effects-': [3084], 'propensity': [3088], 'effects,': [3097], 'demonstrate': [3114], 'toxicities': [3116], 'marimastat': [3122], 'Sprague-Dawley': [3154], '(6/sex)': [3156], '2000': [3160, 3190], 'maximum': [3169], 'feasible': [3170], 'dose)': [3171], 'period': [3174], 'weeks.': [3177], 'third': [3179], 'group': [3180, 4000, 4027, 4420], 'given': [3183], 'single': [3185], 'oral': [3187, 3259], 'dose': [3188], 'hydroxamic': [3195, 3595, 4020], '4,': [3200], '(R)-2-(4′-bromobiphenyl-4-sulfonylamino)-N-hydroxy-3-methylbutyramide': [3201], "(23O'Brien": [3202], 'P.M.': [3203], 'Ortwine': [3204], 'D.F.': [3205], 'Pavlovsky': [3206], 'A.G.': [3207], 'Picard': [3208], 'Sliskovic': [3210], 'D.R.': [3211], 'Roth': [3212], 'B.D.': [3213], 'Dyer': [3214], 'R.D.': [3215], 'Johnson': [3216], 'Man': [3218], 'C': [3219], 'Med.': [3221], '43:': [3224], '156-166Crossref': [3225], '(112)': [3228], 'served': [3231], 'positive': [3234], 'control.': [3235], 'calcaneon': [3237], 'tendon': [3238], 'femorotibial,': [3240], 'tibiotarsal,': [3241], 'humeroradial': [3243], 'prepared': [3246], 'bilaterally': [3247], 'microscopic': [3249], 'assessment': [3250], 'potential': [3252], 'joint-related': [3253], 'lesions.': [3254], '14': [3256], 'days': [3257], 'dosing': [3260], 'either': [3264], 'vehicle,': [3265], 'representative': [3276], 'samples': [3277, 3464], 'femorotibial': [3279], 'necropsy,': [3284], 'fixed': [3285], 'neutral-buffered': [3288], 'formalin,': [3289], 'decalcified,': [3290], 'processed': [3292], 'hematoxylin': [3294], 'eosin': [3296], 'microcopy': [3299], 'any': [3302], 'compound-induced': [3303], 'changes': [3304], 'histology.': [3307], 'Statistical': [3308, 3424], 'Analyses-For': [3309], 'models': [3327, 3947, 4194], 'program': [3340], 'globally': [3341], 'fits': [3342], 'provides': [3352], 'X2': [3355, 3877, 3953], 'value': [3356, 3878], 'representing': [3357], 'goodness': [3359], 'model.': [3368], 'statistical': [3371, 3438, 3468], 'analysis': [3372, 3387, 3460], 'animal': [3374], 'data,': [3376], 'SigmaStat®': [3377], '(Jandel': [3379], 'Scientific,': [3380], 'Rafael,': [3382], 'CA)': [3383], 'used.': [3385, 3834], 'One-way': [3386], 'variance': [3389, 3455], 'carried': [3391, 3429, 3740, 3764], 'see': [3394, 3408], 'if': [3395, 3409], 'differences': [3396], 'existed': [3397], 'among': [3398], 'experimental': [3400, 3415], 'groups,': [3401, 3449], "Dunnett's": [3403], 'mean': [3411], 'responses': [3412], 'groups': [3416], 'statistically': [3418], 'significantly': [3419], 'group.': [3423], 'tests': [3425, 3456, 3763], 'two-tailed': [3427], 'p': [3433], '0.05': [3435], 'significance.': [3439], 'study': [3443], 'consisted': [3444], 'normality': [3452], 'indicated': [3461, 4165], 'satisfied': [3465], 'standard': [3467], 'assumptions': [3469], 'required.': [3470], 'Discovery': [3471], 'Biochemical': [3473], 'Characterization': [3474], 'Inhibitors-We': [3477], 'screened': [3478], 'compound': [3480], 'library': [3481], 'hydrolytic': [3486], '(6-benzyl-5,7-dioxo-6,7-dihydro-5H-thiazolo[3,2-c]pyrimidine-2-carboxylic': [3495], 'benzyl': [3497], 'ester)': [3498], 'potent': [3502], '(Fig.': [3512, 4146, 4283], '1A).': [3513], 'Remarkably,': [3514], 'nine': [3526], 'MMPs,': [3528], 'novel': [3533], 'chemotype': [3535], 'did': [3536, 4168], 'closely': [3540], 'related': [3541], '(Table': [3543], '1).': [3544], 'Also': [3545], 'highlighted': [3546], 'Table': [3548, 3758, 4253], 'improved': [3552], 'potency': [3553], '(IC50': [3554], '0.67': [3556], 'extremely': [3559], 'advanced': [3566], 'derivative,': [3567], '(4-[1-methyl-2,4-dioxo-6-(3-phenyl-prop-1-ynyl)-1,4-dihydro-2H-quinazolin-3-ylmethyl]-benzoic': [3570], 'acid).': [3571], 'Compounds': [3576, 4067, 4226, 4258], 'stark': [3584], 'contrast': [3585], '3,': [3593], 'acid-containing': [3596], 'broad-spectrum': [3597], 'GM-6001,': [3602], 'Galardin.': [3604], 'isolated': [3610], 'ADAMTS4': [3612], '-5': [3614], 'vitro': [3617], 'native': [3622], 'aggrecan': [3623], 'BC-3': [3629], 'antibody,': [3631], 'showed': [3634, 3749, 3777, 3802], '>': [3636], 'aggrecanases.': [3643], '4G.': [3644], 'Munie,': [3645], 'Wittwer,': [3647], 'Tortorella,': [3650], 'unpublished': [3651, 3979, 4425], 'data.TABLE': [3652], '1Contrasting': [3653], '(GM-6001)': [3671], 'triplicate': [3681], 'titrations': [3683], 'thiopeptolide': [3686], 'Scholar).*,': [3701], 'precipitation': [3704, 3722], 'observed': [3706, 3724, 4447], '100,000': [3711, 3729], 'nm.': [3712, 3730], 'Open': [3713], 'table': [3714], 'new': [3717, 4163], 'tab': [3718], '*,': [3719], 'some': [3732], 'assays,': [3737], '7': [3744], 'buffer,': [3746], 'visible': [3750], 'insolubility': [3751, 3806], 'μm,': [3754, 3783, 3810, 3872], 'noted': [3756], 'routine': [3761], 'solubility': [3762, 3778, 3822], 'phosphate': [3767, 3788], '7.5': [3771], '6.5,': [3773], 'however,': [3774], 'less': [3780, 3950], 'μm.': [3795], 'hand,': [3801], 'no': [3803], 'sign': [3804], 'highest': [3812], 'assays.': [3819], 'sensitive': [3827], 'system': [3831], 'steady-state': [3836], 'experiments,': [3838], 'linear': [3843, 3971], '(Figs.': [3848], 'B': [3850], 'C)': [3852], '64': [3856], 'nm,': [3859], '402': [3862], 'pmol': [3865], 'min–1,': [3866], '48': [3869], 'goodness-of-fit': [3875], '0.0262.': [3880], 'independently': [3890], 'simultaneously': [3892], 'non-overlapping': [3897], 'sites,': [3898], 'binds': [3902, 4001, 4029], 'affinity': [3905, 3925], 'free': [3908], 'enzyme·substrate': [3913], 'complex.': [3914], 'alter': [3922], 'binding': [3924, 4039, 4087, 4189, 4208, 4296, 4451], 'vice': [3930], 'versa.': [3931], 'Attempts': [3932], 'equations': [3940], 'mixed,': [3942], 'competitive,': [3943], 'uncompetitive': [3945], 'resulted': [3948], 'satisfactory': [3951], 'values': [3954], '0.0270,': [3956], '0.2947,': [3957], '0.1439,': [3959], 'respectively.': [3960, 4243], '5A.': [3976], 'Johnson,': [3978], 'observations.': [3980, 4426], 'MMP-catalyzed': [3982], 'peptide': [3983, 4086], 'bond': [3984], 'hydrolysis,': [3985], 'thought': [3988], 'carbonyl': [3991], 'oxygen': [3992], 'atom': [3993], 'oxyanion': [3995], 'scissile': [3998], 'amide': [3999], 'to,': [4002], 'polarized': [4005], 'ion.': [4010, 4175], 'Nearly': [4011], 'date': [4017], 'possess': [4018], 'carboxylic': [4022], 'metal-chelating': [4026], 'ion': [4034, 4082], 'competes': [4036], '(24Skotnicki': [4040], 'J.S.': [4041], 'DiGrandi': [4042], 'M.J.': [4043], 'Levin': [4044], 'J.I.': [4045], 'Curr.': [4046], 'Drug': [4048], 'Discov.': [4049], 'Devel.': [4050], '6:': [4052], '742-759PubMed': [4053], 'contrast,': [4057], 'displayed': [4065], 'indicates': [4071], 'cleft.': [4090], 'confirmed': [4092], 'rapidly': [4101], 'fully': [4103], 'enzyme-inhibitor': [4106], 'preincubation-dilution': [4107], 'studies.5': [4109], 'physiologically': [4119], 'relevant': [4120, 4440], 'macromolecular': [4121], 'retains': [4130], 'potently': [4134], 'proteolysis': [4137], '51': [4142], '2).': [4147], 'Crystal': [4148], 'Structures': [4149], 'Inhibitors': [4151], 'Bound': [4152], 'MMP13-The': [4154], 'chemotypes': [4164], 'could': [4178], 'use': [4180], 'reliable': [4193], 'predict': [4196], 'bind.': [4201], 'We,': [4202], 'therefore,': [4203], 'mode': [4206], 'MMP13CD.': [4217], '6The': [4218], 'atomic': [4219], 'complex': [4224, 4264], 'deposited': [4232], 'Protein': [4235], 'Bank': [4237], 'entries': [4239], '2OW9': [4240], '2OZR,': [4242], 'collection': [4246, 4472, 4479], 'statistics': [4249], 'reported': [4251], 'co-crystals': [4256], 'acetohydroxamic': [4268], 'ligand': [4271], 'autolysis.': [4275], 'secondary': [4277], 'tertiary': [4279], 'structures': [4280], '3A)': [4284], 'general': [4286], 'resemble': [4287], 'those': [4288, 4395], 'crystallized': [4293], '(25Roswell': [4298], 'Hatwin': [4300], 'Minshull': [4302], 'C.A.': [4303], 'Jepson': [4304], 'Brockbank': [4306], 'S.M.V.': [4307], 'Barratt': [4308], 'D.G.': [4309], 'Slater': [4310], 'A.M.': [4311, 4317], 'McPheat': [4312], 'W.L.': [4313], 'Waterson': [4314], 'Henney': [4316], 'Pauptit': [4318], 'R.A.': [4319], 'Mol.': [4321, 4346], '2002;': [4323], '319:': [4324], '173-181Crossref': [4325], '(188)': [4328], '26Lang': [4331], 'Kocourek': [4333], 'Braun': [4335], 'Huber': [4339], 'Bode': [4341], 'Maskos': [4343], 'K.': [4344], '312:': [4349], '731-742Crossref': [4350], '(96)': [4353], 'except': [4356], 'N-terminal': [4359], 'region': [4360], 'S1′-specificity': [4367, 4435, 4462], 'loop': [4368, 4436, 4463], '(S1′': [4369], 'nomenclature': [4370], '(27Schechter': [4371], 'I.': [4372], 'Berger': [4373], '1967;': [4379], '27:': [4380], '157-162Crossref': [4381], '(4755)': [4384], 'Scholar)).': [4386], 'prepared,': [4393], 'including': [4394], 'here,': [4397], 'N': [4399], 'terminus': [4400], 'can': [4404], 'adopt': [4405], 'orientations': [4407], 'depending': [4408], 'used,': [4412], 'crystallization': [4414], 'conditions,': [4415], 'and/or': [4416], 'resultant': [4418], 'observed.': [4421], '7A.': [4422], 'Pavlovsky,': [4424], 'disposition': [4432], 'discovery': [4444], 'efforts.': [4445], 'non-zinc': [4450], 'confer': [4456], 'ordered': [4458], 'otherwise': [4466], 'flexible': [4467], 'poorly': [4469], 'defined.TABLE': [4470], '2Data': [4471, 4478], 'statisticsCompound': [4476], '1Compound': [4477], 'Wavelength': [4480], '(Å)1.00': [4481], 'Source/detectorAPS': [4482], '17-ID/MARCCD-165APS': [4483], 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