Identification of circadian clock modulators from existing drugs

Name: Work Video:
Duration: 3 min 30 s
T. Katherine Tamai; Yusuke Nakane; Wataru Ota; Akane Kobayashi; M. Ishiguro; Naoya Kadofusa; Keisuke Ikegami; Kazuhiro Yagita; Yasufumi Shigeyoshi; Masaki Sudo; Taeko Nishiwaki‐Ohkawa; Ayato Sato; Takashi Yoshimura
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'letters,': [909], 'reviewer': [910], 'comments': [911], 'responses': [914], 'to': [915, 918, 932, 942, 959, 1040, 1049, 1086, 1111, 1155, 1184, 1297, 1326, 1335, 1367, 1451, 1473, 1491, 1519, 1525, 1539, 1621, 1668, 1716, 2292, 2586, 2597, 2664, 2762, 2846, 2856, 2876, 2891, 2901, 2920, 2949, 2970, 2981, 3004, 3027, 3034, 3039, 3051, 3089, 3184, 3211, 3230, 3234, 3270, 3279, 3289, 3298, 3316, 3321, 3338, 3341, 3357, 3373, 3397, 3408, 3427, 3433, 3439, 3472, 3484, 3518, 3524, 3533, 3546, 3561, 3571, 3634, 3666, 3700, 3865, 3875, 3900, 3911, 3982, 3991, 4029, 4046, 4058], 'feedback.': [916], 'ToolsAdd': [917], 'favoritesDownload': [919], 'CitationsTrack': [920], 'CitationsPermissions': [921], 'ShareFacebookTwitterLinked': [922], 'InMendeleyWechatReddit': [923], 'Figures': [924], '&': [925, 1529, 1980, 3619], 'Info': [926], 'Abstract': [927], 'Chronic': [928, 1099, 1355, 3265, 3988], 'disruption': [930], 'due': [931, 1325], 'shift': [933, 1327, 3428, 3526, 3585, 3631], 'work': [934, 1328], 'or': [935, 1329, 1338, 1401, 1468, 1507, 1766, 1769, 1774, 1835, 2099, 2103, 2107, 2111, 2115, 2166, 2294, 2304, 2309, 2515, 2616, 2750, 2898, 2933, 3168, 3177, 3249, 3600, 3658, 3669, 4248, 4269, 4325], 'frequent': [936], 'travel': [937, 1330, 3667], 'across': [938, 1331], 'time': [939, 1332, 1351, 3332, 3515], 'zones': [940, 1333], 'leads': [941, 1110, 1334, 1366, 3990, 4045], 'jet-lag': [943, 3161, 3191, 3201, 3340, 3540, 3636, 3654, 3683], 'an': [945, 1131, 1368, 1709, 2285, 3388, 3473, 3534], 'increased': [946, 1112, 1369, 2585, 2948], 'risk': [947, 1113, 1370], 'diabetes,': [949, 1116, 1372], 'cardiovascular': [950, 1117, 1373, 1911], 'disease,': [951], 'cancer.': [953, 1120], 'The': [954, 1289, 1483], 'development': [955, 1484], 'new': [957, 1088, 1186, 1452, 1486, 1509, 1541, 1676, 1682, 1718, 3185, 3291, 3364, 3399, 3435], 'pharmaceuticals': [958], 'treat': [960], 'disorders,': [962], 'however,': [963, 2227], 'is': [964, 1015, 1027, 1082, 1180, 1494, 1514, 1664, 1970, 2150, 2261, 2274, 2478, 2535, 2652, 2726, 3049, 3146, 3580, 3610, 3748, 3819, 3970, 4178, 4199, 4290], 'costly': [965, 1495], 'hugely': [967, 1497], 'time-consuming.': [968], 'We': [969, 1532, 1565, 2776, 2868, 3219, 3326], 'therefore': [970, 1515], 'performed': [971, 3199], 'high-throughput': [973, 1535], 'chemical': [974, 1399, 1536, 1573, 1638], 'screen': [975, 1059, 1639, 1811, 1992, 2131, 2185], 'in': [983, 1024, 1033, 1075, 1149, 1174, 1199, 1210, 1239, 1314, 1606, 1608, 1655, 1733, 1743, 1808, 1836, 1924, 1945, 1990, 1995, 2073, 2128, 2142, 2152, 2163, 2183, 2216, 2266, 2347, 2405, 2440, 2480, 2537, 2558, 2571, 2654, 2688, 2728, 2765, 2772, 2806, 2822, 2831, 2850, 2966, 3015, 3101, 3148, 3162, 3275, 3312, 3348, 3423, 3457, 3503, 3507, 3696, 3750, 3766, 3821, 3972, 3996, 3999, 4011, 4017, 4039, 4052, 4071, 4081, 4098, 4141, 4167, 4188, 4196, 4239, 4292], 'human': [984, 1688], 'U2OS': [985, 1690, 2074, 2217, 2316, 2406, 2441, 2766, 4240], 'cells,': [986, 2767], 'with': [987, 1499, 1557, 1817, 2318, 2680, 2759, 2791, 2937, 3252, 3353, 3467, 3541], 'aim': [989, 1559], 'repurposing': [991, 1081, 1124, 1179, 1561, 1663], 'known': [992, 1011, 1562, 1975, 1984, 3050, 4179], 'bioactive': [993, 1563], 'compounds.': [994, 1564, 2198], 'Approximately': [995, 1136], '5%': [996, 1137], 'screened': [1000, 1140, 1704, 2072], 'altered': [1001, 1142, 1596, 1839], 'period,': [1003, 1598, 2188, 2313, 2696, 3179, 4092], 'period-shortening': [1006, 1601, 3642], 'compound': [1007], 'dehydroepiandrosterone': [1008, 1126], '(DHEA;': [1009], 'also': [1010, 1060, 1256, 1448, 1640, 1797, 2869], 'as': [1012, 1029, 1130, 1630, 2284, 2356, 2385, 2508, 2623, 2701, 3225, 4318], 'prasterone).': [1013], 'DHEA': [1014, 1039, 1145, 1157, 1610, 1627, 2174, 2203, 2207, 2234, 2260, 2302, 2394, 2411, 2424, 2431, 2488, 2497, 2564, 2673, 2687, 2742, 2768, 2817, 2836, 2854, 2939, 2951, 2961, 2995, 3048, 3097, 3159, 3208, 3268, 3334, 3354, 3392, 3454, 3468, 3517, 3681, 3687, 3757, 3828, 3892, 3989, 4014, 4043], 'one': [1016, 1856, 2275, 2305, 4245], 'most': [1019, 2278], 'abundant': [1020, 2279], 'circulating': [1021, 2280], 'steroid': [1022, 2201, 2263, 2321, 2399], 'hormones': [1023, 1889, 2322, 2344], 'humans': [1025], 'available': [1028, 1466], 'dietary': [1031, 3542], 'supplement': [1032], 'USA.': [1035], 'Dietary': [1036, 3156, 3678], 'administration': [1037, 3157, 3266, 3679, 3688], 'mice': [1041, 1607, 2787, 2832, 2875, 2967, 3163, 3221, 3242, 3386, 3415, 3466, 3697, 3767, 4006], 'shortened': [1042, 1146, 1158, 1612, 1770, 2108, 2186, 2403, 2769, 4090], 'free-running': [1043, 2922, 3616], 'period': [1045, 1148, 1160, 1614, 1757, 1763, 1771, 2178, 2215, 2240, 2337, 2364, 2375, 2404, 2418, 2427, 2439, 2607, 2771, 2805, 2821, 3007, 3121, 3617, 4225, 4255, 4313], 'accelerated': [1047, 1619], 're-entrainment': [1048, 1450, 1620, 3183, 3210, 3532, 3665, 3699, 4028], 'advanced': [1050, 1622, 3259, 3474, 3535], 'light–dark': [1051, 1453, 2893, 3186], '(LD)': [1052, 1454, 3187], 'cycles,': [1053, 1624, 3188], 'thereby': [1054, 3189, 3538], 'reducing': [1055, 3190, 3539], 'jet-lag.': [1056, 1164, 1482, 1636], 'Our': [1057, 1637], 'drug': [1058, 1080, 1123, 1489, 1662, 1711, 1926, 2005, 2350, 2602, 2888, 3043], 'revealed': [1061, 1871], 'involvement': [1063], 'tyrosine': [1065, 1166, 1643, 4076, 4112, 4158, 4230], 'kinases,': [1066], 'ABL1': [1067], 'ABL2,': [1069], 'BCR': [1072, 1169, 4069, 4193, 4221], 'serine/threonine': [1073, 1170], 'kinase': [1074, 1171, 1414, 1421, 1644, 4077, 4113, 4159, 4231], 'regulating': [1076, 1175, 1946], 'period.': [1078, 1144, 1177, 1660, 1826, 1841, 2120, 2924], 'Thus,': [1079, 1661, 1827, 3510], 'useful': [1084, 1182, 1666], 'approach': [1085, 1183, 1518], 'identify': [1087, 1185, 1669, 1717], 'potential': [1093, 1522, 1670, 1752, 1802, 2092], 'therapies': [1094], 'disorders.': [1097], 'Synopsis': [1098], 'misalignment': [1101, 1357, 1674], 'has': [1102, 1358, 3499], 'long': [1103], 'term': [1104], 'consequences': [1105, 1360, 1480, 4182], 'on': [1106, 1361, 1756, 1832, 1846, 2193, 2362, 2416, 2437, 2489, 2498, 2611, 2694, 2743, 3000, 3067, 3098, 3209, 3596, 3693, 3763, 3837, 4024, 4149, 4161, 4236, 4305], 'our': [1107, 1217, 1362, 1960, 1991, 2184, 2348, 2763, 4082], 'health': [1108, 1363], 'developing': [1115], 'disease': [1118, 1374], 'Using': [1121, 1686], 'approach,': [1125], '(DHEA)': [1127], 'was': [1128, 2395, 2569, 2608, 2946, 3125, 3258, 3355, 3522, 3732, 3849, 3936, 4015, 4256], 'identified': [1129, 1393, 1591, 1641, 1750, 1923, 1989, 2090, 2182, 2355, 4080], 'important': [1132], 'modulator.': [1135], 'cells': [1150, 1255, 2077, 2218, 2317, 2442, 2677, 2823], 'tissues.': [1152], 'When': [1153, 1604], 'fed': [1154, 2884, 3220], 'mice,': [1156, 3283, 3308, 4041], 'significantly': [1162, 1403, 1611], 'reduced': [1163], 'ABL1/2': [1165], 'kinases': [1167, 1654, 4070, 4222], 'are': [1172, 1193, 1227, 1274, 1462, 1993, 2007, 2140, 2449, 2506, 2699, 3569, 3632, 3858, 4106, 4131, 4164, 4252, 4262, 4316], 'involved': [1173], 'Drug': [1178, 1505, 1579, 1586, 2057, 2066], 'modulators.': [1189, 1721], 'Introduction': [1190], 'Circadian': [1191, 4254], 'clocks': [1192, 1205, 2905, 3568], 'highly': [1194], 'conserved,': [1195], 'endogenous': [1196, 2320, 2398], 'timers': [1197], 'present': [1198], 'virtually': [1200], 'all': [1201, 1729, 2136, 2147], 'living': [1202], 'organisms.': [1203], 'These': [1204, 2326, 2813, 2991, 3382, 3493, 4035, 4104], 'regulate': [1206], 'near': [1207], '24-h': [1208], 'rhythms': [1209, 1226, 1617, 1948, 3014, 3100, 3422, 4238, 4309], 'numerous': [1211], 'behavioral': [1212, 1477], 'physiological': [1214], 'processes,': [1215], 'sleep–wake': [1218], 'cycles': [1219, 1455], 'metabolism.': [1221], 'In': [1222, 1998, 2258, 2369, 3281, 3306, 3418, 3575, 3590], 'mammals,': [1223], 'these': [1224, 1800, 1860, 1918, 2197, 2343, 2809, 2958, 3061], 'daily': [1225], 'controlled': [1228], 'central': [1231, 1896], 'pacemaker,': [1233], 'suprachiasmatic': [1235], 'nucleus': [1236], '(SCN),': [1237], 'located': [1238], 'anterior': [1241], 'hypothalamus': [1242], '(Ralph': [1243], 'et': [1244, 1248, 1262, 1266, 1270, 1378, 1382, 1386, 1425, 1429, 1433, 1457, 1546, 1550, 1554, 1700, 1934, 1955, 2245, 2249, 2842, 2974, 3058, 3084, 4124, 4173, 4204, 4208, 4212], 'al,': [1245, 1249, 1263, 1267, 1271, 1379, 1383, 1387, 1426, 1430, 1434, 1458, 1547, 1551, 1555, 1701, 1935, 1956, 2246, 2250, 2843, 2975, 3059, 3085, 4125, 4174, 4205, 4209, 4213], '1990;': [1246], 'Klein': [1247], '1991).': [1250], 'Most': [1251, 4127], 'peripheral': [1252], 'tissues': [1253, 2810], 'contain': [1257], 'self-sustained': [1258], 'oscillators': [1260], '(Balsalobre': [1261], '1998;': [1264], 'Yamazaki': [1265], '2000;': [1268], 'Yoo': [1269], '2004),': [1272], 'which': [1273, 2252, 3566, 4142], 'driven': [1275], 'transcriptional–translational': [1277], 'feedback': [1278], 'loops': [1279], 'composed': [1280], 'genes': [1284, 1395], 'proteins': [1286, 1292], '(Takahashi,': [1287], '2015).': [1288, 1531, 1982], 'basic': [1290], 'helix-loop-helix': [1291], 'CLOCK': [1293], 'BMAL1': [1295], 'heterodimerize': [1296], 'form': [1298], 'transcriptional': [1300], 'activator': [1301], 'complex': [1302, 1476], 'activate': [1304], 'PER': [1306], 'CRY': [1308], 'repressor': [1309], 'genes,': [1310], 'whose': [1311, 1787], 'protein': [1312, 4187], 'products,': [1313], 'turn,': [1315], 'repress': [1316], 'their': [1317, 2360, 2903, 3236], 'own': [1318], 'transcription.': [1319], 'Disruption': [1320], 'desynchrony,': [1337], 'jet-lag,': [1339, 1405], 'reflects': [1341], 'mismatch': [1343], 'between': [1344], 'internal': [1346], 'biological': [1347], 'external': [1350], 'cues': [1352], '(Arendt,': [1353], '2009).': [1354], 'long-term': [1359], 'often': [1365], 'cancer': [1376], '(Davidson': [1377], '2006;': [1380], 'Scheer': [1381], '2009;': [1384, 1552], 'Buxton': [1385], '2012).': [1388], 'Recent': [1389, 2225], 'studies': [1391, 2830], 'have': [1392, 1920, 1942, 1974, 2228, 2254, 2833, 2962, 3558], 'several': [1394, 1642, 1751, 2319], 'that': [1396, 1595, 1626, 1646, 1760, 1941, 1971, 2095, 2230, 2329, 2402, 2816, 2835, 2994, 3064, 3175, 3385, 3496, 3624, 3648, 4087], 'mutation,': [1398], 'inhibition': [1400], 'knockdown,': [1402], 'reduce': [1404, 1723, 3339, 3635, 3653], 'vasopressin': [1408], 'V1a': [1409], 'V1b': [1411], 'receptors,': [1412], 'casein': [1413], '1': [1415, 1422, 1741, 1765, 2023, 2084, 2098, 2379, 2604, 2897, 2918], 'epsilon': [1416], '(CK1ε),': [1417], 'salt': [1419], 'inducible': [1420], '(Sik1;': [1423], 'Jagannath': [1424], '2013;': [1427, 1431], 'Yamaguchi': [1428], 'Pilorz': [1432], '2014).': [1435], 'Injection': [1436], 'neuropeptide': [1439], 'vasoactive': [1440], 'intestinal': [1441], 'polypeptide': [1442], '(VIP)': [1443], 'into': [1444, 2562, 2578, 2874, 2912, 3489, 3916, 3947], 'mouse': [1446, 2490, 2755], 'SCN': [1447, 2499, 2782, 3073], 'accelerates': [1449], '(An': [1456], '2013).': [1459], 'However,': [1460], 'there': [1461], 'currently': [1463, 1831], 'no': [1464, 2414], 'orally': [1465, 2840], 'supplements,': [1469], 'except': [1470], 'melatonin': [1471], 'perhaps,': [1472], 'combat': [1474], 'metabolic': [1479], 'pharmaceuticals,': [1487], 'discovery': [1490], 'market': [1492, 1834], 'approval,': [1493], 'time-consuming': [1498], 'high': [1501, 2231], 'rate': [1502, 3601], 'failure.': [1504], 'repurposing,': [1506], 'identifying': [1508], 'functions': [1510, 2283], 'compounds,': [1513, 1804, 1877, 2358], 'popular': [1517], 'fast': [1520], 'track': [1521], 'through': [1524, 3079, 3637], 'clinical': [1526, 1837], 'trials': [1527, 1838], '(Rennekamp': [1528, 1979], 'Peterson,': [1530, 1981], 'used': [1533], 'screening': [1537, 1749, 1961, 1967, 2049, 2089], 'strategy': [1538, 1667], 'isolate': [1540], '(Hirota': [1545], '2008;': [1548], 'Isojima': [1549], 'Chen': [1553], '2011),': [1556], 'tested': [1566, 1605, 1732, 2401, 2965], 'over': [1567, 1705], '1,000': [1568, 1706], 'small': [1569], 'molecules': [1570, 1707], 'two': [1572, 1736, 4004], 'libraries,': [1574], 'US': [1576, 2054], 'Food': [1577, 2055], 'Administration': [1580, 2058], '(FDA)-approved': [1581, 2059], 'International': [1585, 2065], 'Collection': [1587, 2067], '(IDC),': [1588], 'we': [1590, 1703, 2190, 2253, 2314, 2752, 2799, 2852, 3198, 3463], 'nearly': [1592], '60': [1593], 'chemicals': [1594, 1819, 2181], 'molecule': [1602], 'DHEA.': [1603, 2760, 2792, 3543], 'vivo,': [1609, 2851], 'locomotor': [1616], 'LD': [1623, 2559, 3215, 3232, 3256, 3292, 3302, 3345, 3365, 3400, 3436, 3475, 3536, 3573, 3704, 3772, 3796, 3867, 3880, 3904, 3942, 4033], 'suggesting': [1625], 'might': [1628, 1862, 3076, 3181, 3335, 3652], 'serve': [1629], 'convenient': [1632], 'over-the-counter': [1633], 'treatment': [1634, 1852, 3331, 3352, 3455, 3514, 4044, 4117], 'inhibitors': [1645, 4078, 4108, 4232], 'modulated': [1647], 'function,': [1649], 'implicating': [1650], 'class': [1652], 'control': [1657, 2545, 3108, 3414, 3508, 3710, 3778, 3922], 'treatments': [1671], 'regulators.': [1678], 'Results': [1679], 'osteosarcoma': [1689], 'cell': [1691, 2748], 'line': [1692, 4023], 'stably': [1693], 'expressing': [1694], 'reporter': [1697, 2076], 'Bmal1-dLuc': [1698, 4237, 4308], '(Oshima': [1699], '2015),': [1702, 3060], 'FDA-approved': [1710], 'library': [1712], 'IDC': [1715], 'To': [1722, 2299, 2736, 3194, 3450], 'number': [1725], 'false': [1727], 'positives,': [1728], 'compounds': [1730, 1754, 1823, 1919, 1988, 2094, 2126, 2139, 2161, 2387, 3623, 3645, 3647], 'were': [1731, 1779, 1789, 1796, 1806, 2071, 2345, 2353, 2365, 2382, 2459, 2520, 2594, 2631, 2678, 2710, 2747, 2797, 2882, 2909, 2926, 2978, 3069, 3243, 3370, 3481, 3804, 3955, 4079, 4096, 4274], 'triplicate': [1734], 'at': [1735, 2078, 2102, 2114], 'different': [1737, 1873], 'concentrations': [1738, 2796, 2959], '(10': [1739], 'μM)': [1742, 2237], '384-well': [1745], 'plate': [1746], 'format.': [1747], 'Primary': [1748, 2088], 'hit': [1753, 1803, 1876, 1987, 2093, 2125, 2138, 2160, 2357, 2386], 'based': [1755, 2610], 'change.': [1758], 'Drugs': [1759], 'lengthened': [1761, 2096, 2335, 2374, 4088], 'hours': [1768, 1776], '0.5': [1773, 2110], '(Fig': [1777, 1913, 2044, 2219, 2256, 2774, 2811, 2906, 3192, 3217, 3263, 3304, 3324, 3367, 3416, 3491, 4102], '1A)': [1778], 'selected': [1780], 'additional': [1782], 'screening,': [1783], 'although': [1784], 'some': [1785, 1916, 2195, 3307, 4000, 4040], 'chemicals,': [1786], 'effects': [1788, 2361, 2436, 2693, 2740, 2849, 3066, 3206, 4227], 'clearly': [1790], 'dose-dependent': [1791, 2211, 2435, 3017], 'but': [1792, 2352, 3294], 'below': [1793, 2116, 2366], 'threshold': [1794, 2367], 'values,': [1795], 'included.': [1798], 'Of': [1799], '72': [1801, 2091], '59': [1805, 2124, 2137], 'validated': [1807, 2127], 'secondary': [1810, 2130], 'dose-dependency': [1813, 2133], '(Appendix': [1814, 2296, 2338, 2388, 2419], 'Fig': [1815, 2144, 2223, 2297, 2339, 2420, 3045, 3448, 4012], 'S1),': [1816], '46': [1818], 'lengthening': [1820], '13': [1822], 'shortening': [1824, 2212, 2802], '~5%': [1828], 'This': [1842, 2944], 'indicates': [1843], 'that,': [1844, 4038], 'depending': [1845], 'dose': [1848, 2945, 3390], 'duration': [1850, 3853], 'other': [1854], 'ailments,': [1855], '"side': [1857], 'effect"': [1858], 'be': [1863, 2290, 2838, 2971, 3077, 3336], 'perturbation': [1864], 'clock.': [1868], 'Therapeutic': [1869, 2121], 'classification': [1870, 2122], 'eight': [1872], 'categories': [1874, 2003], '(i)': [1879], 'anti-cancer': [1880], 'immunosuppressive': [1882], 'drugs,': [1883, 1904], '(ii)': [1884], 'disinfectants': [1885], 'antiseptics,': [1887], '(iii)': [1888], 'contraceptives,': [1891], '(iv)': [1892], 'targeting': [1894], 'nervous': [1897], 'system,': [1898], '(v)': [1899], 'dermatological': [1900], 'agents,': [1901], '(vi)': [1902], 'gastrointestinal': [1903], '(vii)': [1905], 'vitamins': [1906], 'minerals,': [1908], '(viii)': [1910], 'agents': [1912], '1B).': [1914], 'Importantly,': [1915, 2957], 'been': [1921, 1943, 2963, 3559], 'previously': [1922, 2964], 'screens': [1927], '(i.e.,': [1928, 1949, 3038, 3646], 'DNA': [1929, 2016], 'damage': [1930], 'agent,': [1931], 'mitoxantrone;': [1932], 'Hirota': [1933], '2008),': [1936], 'whereas': [1937, 3641], 'others': [1938], 'affect': [1939, 3649], 'pathways': [1940], 'implicated': [1944], 'EGF': [1950], 'receptor': [1951, 2014, 2021, 2032, 2036], 'inhibitor,': [1952], 'erlotinib;': [1953], 'Kramer': [1954], '2001),': [1957], 'thus': [1958, 3663], 'validating': [1959], 'protocol.': [1962], 'One': [1963], 'obvious': [1964], 'advantage': [1965], 'they': [1972], 'frequently': [1973], 'mechanisms': [1976, 3553, 3564], 'action': [1978], 'All': [1983, 2475, 2532, 2649, 2723, 3143, 3745, 3816, 3967, 4287, 4337], 'targets': [1985, 2006, 2158], 'listed': [1994], 'Table': [1996, 2154, 2482, 2539, 2656, 2730, 3150, 3752, 3823, 3974, 4294], 'EV1.': [1997, 2669], 'addition,': [1999, 3419], 'top': [2001], 'six': [2002, 2157], 'shown': [2008, 2141, 2151, 2229, 2479, 2536, 2653, 2727, 2834, 2969, 3147, 3749, 3820, 3859, 3971, 4010, 4291], 'include': [2010], 'DNA,': [2011], 'androgen': [2013, 2286], '(AR),': [2015], 'topoisomerase': [2017], '2α,': [2018], 'nuclear': [2020], 'subfamily': [2022], 'group': [2024], 'I': [2025], 'member': [2026], '2': [2027, 2899], '(NR1I2),': [2028], 'retinoic': [2030], 'acid': [2031], 'α': [2033], '(RARα)/retinoid': [2034], 'X': [2035], 'β': [2037, 2042], '(RXRβ),': [2038], 'tubulin': [2041], 'chain': [2043], '1C).': [2045], 'Figure': [2046, 2422, 2668, 3093, 3550, 3676, 3986, 4215], '1.': [2047], 'Chemical': [2048, 2428], '(left': [2061, 2614], 'graphs)': [2062, 2070, 2082], '(IDC)': [2068], '(right': [2069, 2619, 3734, 3801, 3952], '10': [2079], 'μM': [2080, 2085, 2487, 2496, 2686], '(top': [2081], '(bottom': [2086], 'graphs).': [2087], '(by': [2097, 2109], 'hours;': [2101, 2113], 'above': [2104], 'red': [2105, 3834], 'line)': [2106, 2118, 2568, 3692], 'blue': [2117], '(data': [2134], 'Appendix': [2143, 2153, 2222, 2481, 2538, 2655, 2729, 3149, 3751, 3822, 3973, 4293], 'S1,': [2145], 'statistical': [2148, 2476, 2533, 2650, 2724, 3144, 3746, 3817, 3968, 4288], 'information': [2149, 2477, 2534, 2651, 2725, 3145, 3747, 3818, 3969, 4289], 'S2).': [2155, 2298, 2340, 2392, 2421], 'Top': [2156], 'reported': [2162], 'DrugBank': [2165], 'KEGG': [2167], 'DRUG': [2168], 'databases.': [2169], 'Download': [2170, 2172, 2658, 2660, 2732, 2734, 3152, 3154, 3672, 3674, 3976, 3978, 4061, 4063], 'figure': [2171, 2659, 2733, 3153, 3673, 3977, 4062], 'PowerPoint': [2173, 2661, 2735, 3155, 3675, 3979, 4064], 'primarily': [2175], 'shortens': [2176, 2425, 2819], 'Relatively': [2179], 'few': [2180], 'so': [2189, 3444], 'initially': [2191, 2883], 'focused': [2192], 'characterizing': [2194], 'Interestingly,': [2199, 2393], 'hormone': [2202, 2264, 2400], 'its': [2205, 2307, 2409, 2434, 2848, 3035, 3065], 'derivative': [2206], 'acetate': [2208], 'showed': [2209], 'clear': [2210], '2A': [2220], 'S1).': [2224], 'reports,': [2226], 'doses': [2232, 2671], '(e.g.,': [2235], '100': [2236, 2685], 'lengthen': [2238, 2674, 3178], 'decrease': [2242], 'amplitude': [2243], '(Rey': [2244], '2016;': [2247], 'Putker': [2248], '2017),': [2251], 'confirmed': [2255], 'EV1).': [2257], 'humans,': [2259], 'produced': [2265], 'adrenal': [2268], 'gland,': [2269], 'gonads,': [2270], 'brain': [2272], 'hormones.': [2281], 'It': [2282], 'precursor': [2287], 'can': [2289, 2837], 'converted': [2291], 'testosterone': [2293, 2334], 'estrogen': [2295], 'determine': [2300, 2737, 3451], 'whether': [2301, 2738, 3328, 3452], 'itself': [2303], 'precursors': [2308], 'metabolites': [2310], 'modulates': [2311, 4223], 'treated': [2315, 2679, 2753, 2789, 3465], 'monitored': [2324], 'bioluminescence.': [2325], 'results': [2327, 2698, 2814, 2992, 3383, 3494, 4036], 'show': [2328, 2692, 2993, 3384, 3495, 4037], 'deoxycorticosterone': [2330], '(21-hydroxyprogesterone),': [2331], '11-deoxycortisol,': [2332], 'Some': [2341], 'included': [2346], 'primary': [2349], 'screen,': [2351, 4083], 'not': [2354, 4200], 'because': [2359], 'values.': [2368], 'contrast,': [2370, 3591], 'progesterone': [2371], '17α-hydroxyprogesterone': [2373], 'than': [2378, 3445, 3506], 'h': [2380, 3262, 3319, 4056], 'indeed': [2383, 2818, 3500], 'classified': [2384], 'Figs': [2389], 'S1': [2390, 4295], 'only': [2397], 'cells.': [2407, 4241], 'Notably,': [2408], 'metabolite': [2410], 'sulfate': [2412], 'had': [2413, 2996], 'effect': [2415, 2999], '2.': [2423], 'structure': [2429], '(left)': [2432, 4310], '(histogram,': [2443], 'right;': [2444], 'luminescent': [2445], 'traces,': [2446], 'below).': [2447], 'Data': [2448, 2505, 2630, 2709, 3803, 3857, 3882, 3954, 4261, 4315], 'mean': [2451, 2510, 2625, 2703, 3885, 4264, 4320], '±': [2452, 2511, 2626, 2704, 3123, 3725, 3799, 3950, 4265, 4321], 'SEM': [2453, 2512, 2627, 2705, 4266, 4322], 'three': [2455, 4247, 4268, 4324], 'independent': [2456, 2517, 3070, 4250, 4271, 4327], 'experiments': [2457, 2518, 4251, 4272, 4328], 'analyzed': [2460, 2521, 2632, 2711, 3129, 3737, 3805, 3956, 4275], 'one-way': [2462, 2713, 4277], 'ANOVA,': [2463, 2635, 2714, 3132, 4278], 'followed': [2464, 2636, 2715, 3133, 4279], "Dunnett's": [2467, 2718, 4282], 'test': [2468, 2642, 2719, 2847, 3139, 3195, 4283], '(*P': [2469, 2526, 2643, 3810, 3961, 4329], '<': [2470, 2473, 2527, 2530, 2644, 2647, 2721, 3141, 3743, 3811, 3814, 3962, 3965, 4285, 4330, 4333], '0.05,': [2471, 2528, 2645, 3812, 3963, 4331], '**P': [2472, 2529, 2646, 3813, 3964, 4332], '0.01).': [2474, 2531, 2648, 2722, 3142, 3744, 3815, 3966, 4286], 'S1.': [2483, 2540, 2657, 3753, 3824, 3975], 'Effect': [2484, 3095, 3684, 3754, 3825, 3889, 4296], '20': [2486], 'embryonic': [2491, 2756], 'fibroblasts': [2492, 2757], '(MEFs)': [2493, 2758], '50': [2495], 'lung': [2501, 2784], 'mPer2Luc': [2503, 2754, 2786], 'mice.': [2504, 3509], 'presented': [2507, 2700, 4317], 'four': [2514, 4249, 4270, 4326], 'five': [2516], "Welch's": [2524, 3740, 3808, 3959, 4335], 't-test': [2525, 3741, 3809, 3960], 'Representative': [2541, 3706, 3774, 3918], 'double-plotted': [2542, 3104, 3707, 3775, 3919], 'actograms': [2543, 3708, 3776, 3920, 4002], '(n': [2546, 2552, 2706, 3109, 3115, 3711, 3717, 3779, 3785, 3923, 3929], '=': [2547, 2553, 2707, 3110, 3116, 3712, 3718, 3780, 3786, 3924, 3930], '8;': [2548, 3111], 'left)': [2549, 3112, 3714, 3782, 3926], 'DHEA-treated': [2551, 3114, 3424, 3504, 3716, 3784, 3928, 4005], '14;': [2554], 'middle)': [2555, 3118, 3720, 3788, 3932], 'animals': [2556, 3425, 3505, 4198], 'entrained': [2557, 3570], 'transferred': [2561, 2911, 3488], 'DD.': [2563, 3917], '(0.5%': [2565], 'w/w;': [2566, 3690, 3833, 4021], 'vertical': [2567, 3691, 4022], 'administered': [2570, 2839, 4016], 'powdered': [2572, 2599, 2857, 2885, 2931, 2934, 2983, 3029, 3223, 3247, 4018], 'food': [2573, 2600, 2858, 2886, 2932, 2935, 2984, 3248, 3250, 3375, 3486, 3913, 4019], '˜1': [2574], 'week': [2575, 2919], 'after': [2576, 3025], 'transfer': [2577, 3915, 3946], 'DD': [2579, 3490, 3948], '6': [2581, 2591, 2942, 2955, 3261], 'days': [2582, 3361, 3406, 3411, 3759, 3830, 3862, 3872, 3894], 'then': [2584, 2595, 2777, 2910, 2927, 2947, 2979, 3371, 3482, 3870, 3909, 3945], '1.0%': [2587, 3761, 3832, 3896], '(w/w)': [2588, 2940, 2952], 'another': [2590, 2954], 'days.': [2592, 2943, 2956, 3479], 'Animals': [2593, 2908, 3480], 'returned': [2596, 2980, 3033, 3372, 3483], 'normal': [2598, 2930, 2982, 3028, 3222, 3246, 3374, 3485, 3912], 'without': [2601, 2887], 'week.': [2605], 'Free-running': [2606, 3120], 'calculated': [2609], 'activity': [2612, 2617, 3010, 3031, 3276, 3313, 3695, 3765, 3997, 4053], 'onset': [2613, 3032, 3277, 3314, 3723, 3791, 3935, 3998, 4054], 'graph)': [2615, 2620], 'offset': [2618], 'plotted': [2622, 3733, 3937], '(far': [2628], 'right).': [2629], 'two-way': [2634, 3131], "Sidak's": [2639, 3136], 'multiple': [2640, 3137], 'comparisons': [2641, 3138], 'Click': [2662, 3087, 3544, 3980], 'here': [2663, 3088, 3545, 3981], 'expand': [2665, 3090, 3547, 3983], 'figure.': [2667, 3092, 3549, 3985], 'High': [2670], 'periodU2OS': [2676], '0,': [2681], '20,': [2682], '50,': [2683], '0.2%': [2689], 'DMSO.': [2690], 'Histograms': [2691], '6).': [2708], '(**P': [2720, 3140, 3742, 4284], 'S2.': [2731, 3151], 'type-': [2749], 'tissue-specific,': [2751], 'Similar': [2761], 'observations': [2764], 'MEFs': [2773], '2B).': [2775, 2812], 'prepared': [2778], 'explant': [2779], 'cultures': [2780], 'them': [2790, 3229, 3471], 'Although': [2793, 3047, 4176], 'slightly': [2794], 'higher': [2795], 'required,': [2798], 'observed': [2800], 'significant': [2801], 'both': [2807, 3009, 4095], 'indicated': [2815], 'tissues,': [2825], 'SCN.': [2828], 'Numerous': [2829], '(Milewich': [2841, 2973], '1995).': [2844, 2976], 'Therefore,': [2845, 3347, 3622], 'added': [2853], 'directly': [2855], 'assessed': [2860], 'function': [2863, 4191], 'monitoring': [2865], 'wheel-running': [2866, 3694, 3764], 'activity.': [2867], 'surgically': [2870], 'implanted': [2871], 'temperature': [2872, 2879, 3013, 3105, 3421, 3839, 3845, 3848], 'devices': [2873], 'measure': [2877, 2921], 'body': [2878, 3012, 3102, 3420, 3838, 3847], 'rhythms.': [2880, 3840], 'Mice': [2881, 2925, 2977, 3369], 'exposed': [2890, 3228, 3470], 'cycle': [2894, 3216, 3233, 3257, 3366, 3401, 3437, 3476, 3797, 3868, 3905, 3943], '(12L:12D)': [2895], 'weeks': [2900], 'entrain': [2902], '2C).': [2907, 3046], 'constant': [2913], 'darkness': [2914], '(DD)': [2915], 'about': [2917, 4180], 'given': [2928, 3244, 3387], 'either': [2929, 3245, 3655], 'mixed': [2936, 3251], '0.5%': [2938], '1%': [2950], 'safe': [2972], 'until': [2985], 'end': [2987], 'experiment.': [2990, 3381, 3856], 'profound': [2998], 'behavior': [3001, 3068], 'appeared': [3003, 3297, 3315, 3426], 'shorten': [3005, 3176], 'manner': [3018], '(Figs': [3019], '2C': [3020], 'EV2,': [3022], 'respectively).': [3023], 'Surprisingly,': [3024], 'return': [3026, 3910], 'food,': [3030, 3224], 'original': [3036], 'phase': [3037, 3041, 3273, 3310, 3525, 3584, 3630, 3730, 3878, 3994, 4050], 'before': [3042], 'treatment;': [3044], 'readily': [3052], 'cross': [3053], 'blood–brain': [3055], 'barrier': [3056], '(Stárka': [3057], 'data': [3062], 'suggest': [3063], 'acting': [3078], 'extra-SCN': [3080], 'pacemaker(s)': [3082], '(Pezuk': [3083], '2010).': [3086], 'EV2.': [3094], 'temperatureRepresentative': [3103], 'records': [3106], '13;': [3117], 'animals.': [3119, 3721, 3789, 3933], '(mean': [3122, 3724, 3798, 3949], 'SEM)': [3124, 3726, 3800, 3951], 'determined': [3126, 4257], '(right)': [3127], 'reduces': [3160, 3682], 'By': [3164], 'temporarily': [3165], 'speeding': [3166], 'up': [3167], 'slowing': [3169, 3659], 'down': [3170, 3660], 'clock,': [3173, 3462, 3607, 3662], 'respectively,': [3180, 4093], 'accelerate': [3182, 3531], 'EV3).': [3193], 'hypothesis,': [3197], 'experiment': [3202, 4009], 'examined': [3204], '6-h': [3213, 3343, 3702, 3729, 3770, 3794, 3877, 3902, 3940, 4031], 'phase-advanced': [3214, 3344, 3703, 3771, 3795, 3903, 3941, 4032], '3).': [3218], 'above,': [3226], 'synchronize': [3235], 'clocks.': [3238], 'After': [3239, 3841], '~1': [3240], 'week,': [3241], 'DHEA,': [3253], '3A).': [3264, 3305], 'led': [3269], 'dramatic': [3272], 'advance': [3274, 3285, 3311, 3459, 3731, 3879, 3995, 4051], 'compared': [3278, 3407, 3438], 'controls.': [3280], 'drug-treated': [3282], 'occurred': [3286], 'almost': [3287], 'immediately': [3288], 'cycle,': [3293, 3537], 'surprisingly,': [3295], 'subsequently': [3296], 'free-run,': [3299], 'even': [3300], 'under': [3301], 'conditions': [3303], 'stabilize': [3317], '~4–6': [3318, 4055], 'prior': [3320, 4057], 'lights': [3322, 4059], 'off': [3323], 'EV4).': [3325], 'wondered': [3327], 'adjusting': [3329, 3512], 'sufficient': [3337], 'cycle.': [3346, 3705, 3773, 3881, 4034], 'next': [3350], 'experiment,': [3351], 'limited': [3356], 'first': [3359], '3': [3360, 3478, 3519], '3B).': [3368, 3417], 'remainder': [3378], 'acute': [3389, 3453, 3756, 3827, 3891], 'shifted': [3393, 3501], 'much': [3394, 4177], 'rapidly': [3396, 3432], 're-entrained': [3403], 'within': [3404], '1–3': [3405], '6–7': [3410], 'required': [3412], 'reset': [3430], 'controls': [3440], '(the': [3441], 'trough': [3442], 'peak;': [3447], '3C).': [3449], 'did,': [3456], 'fact,': [3458], 'again': [3464], '3D).': [3492], 'days,': [3520], 'it': [3521], 'possible': [3523], 'EV3.': [3551], 'Possible': [3552], 'overcoming': [3555], 'jet-lagTwo': [3556], 'models': [3557], 'proposed': [3560], 'explain': [3562], 'environmental': [3572, 3588], 'cycles.': [3574], '"nonparametric': [3577], 'model",': [3578], 'entrainment': [3579, 3609, 3864], 'achieved': [3581, 3611], 'caused': [3586, 4132], 'stimuli.': [3589], '"parametric': [3593], 'model"': [3594], 'focuses': [3595], 'angular': [3598, 3650], 'velocity': [3599], 'motion': [3603], 'modulation': [3613], '(Daan': [3618], 'Aschof,': [3620], '2001).': [3621], 'increase': [3625], 'magnitude': [3627], 'predicted': [3633], 'nonparametric': [3639], 'mechanism,': [3640], 'period-lengthening': [3644], 'velocity)': [3651], 'accelerating': [3657, 3664], 'eastward': [3668], 'westward,': [3670], 'respectively.': [3671], '3.': [3677], 'chronic': [3686, 4042, 4119], '(1.0%': [3689, 4020], 'during': [3698, 3727, 3768, 3792, 3938, 4027], '12;': [3713], '11;': [3719, 3787, 3931], 'Activity': [3722, 3790, 3934], 'panel)': [3735], '(3': [3758, 3829, 3893, 3906], 'w/w)': [3762, 3897], '10;': [3781, 3925], 'panel).': [3802, 3953], 'bar': [3835], 'above)': [3836], 'surgical': [3842], 'implantation': [3843], 'devices,': [3846], 'measured': [3850], '2.5': [3861], '7.5': [3871], 'exposure': [3874, 3899], 'represent': [3883], 'each': [3887], 'treatment.': [3888], 'days)': [3907], 'EV4.': [3987], 'stable': [3993, 4049], 'miceDouble-plotted': [4001], '3A.': [4013], 'right)': [4026], 'relatively': [4048], 'off.': [4060], 'Involvement': [4065], 'ABL': [4067, 4195, 4219], 'clockwork': [4074], 'Two': [4075], 'dasatinib': [4084, 4233], 'nilotinib,': [4086], 'effective': [4097], 'nanomolar': [4100], 'range': [4101], '4A).': [4103], 'second-generation': [4107], 'BCR-ABL': [4111, 4171, 4185, 4229], 'approved': [4115], 'myelogenous': [4120], 'leukemia': [4121], '(CML;': [4122], 'Molica': [4123], '2017).': [4126], 'cases': [4128], 'CML': [4130], 'chromosomal': [4135], 'translocation,': [4136], 'called': [4137], 'Philadelphia': [4139], 'chromosome,': [4140], 'break': [4144], 'point': [4145], 'cluster': [4146], '(BCR)': [4147], 'gene': [4148, 4160], 'chromosome': [4150, 4162], '22': [4151], 'Abelson': [4154], '(ABL)': [4155], 'non-receptor': [4156], 'type': [4157], '9': [4163], 'fused,': [4165], 'resulting': [4166], 'chimeric': [4169], 'oncogene,': [4170], '(Faderl': [4172], '1999).': [4175], 'fusion': [4186], 'CML,': [4189], 'intact': [4197], 'well': [4201], 'understood': [4202], '(Schwartzberg': [4203], '1989;': [4206], 'Tybulewicz': [4207], '1991;': [4210], 'Voncken': [4211], '1996).': [4214], '4.': [4216], 'Inhibition': [4217], 'Dose-dependent': [4226], 'nilotinib': [4235], 'Luminescent': [4242], 'traces': [4243], 'shown.': [4253], 'curve': [4259], 'fitting.': [4260], 'siRNA-mediated': [4298], 'knockdown': [4299], 'ABL,': [4301], 'BCR,': [4302], 'SRC': [4304], 'rhythms:': [4307], '(right).': [4314], '0.01,': [4334], 't-test).': [4336], 'sta': [4338]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2801091865', 'counts_by_year': [{'year': 2024, 'cited_by_count': 5}, {'year': 2023, 'cited_by_count': 5}, {'year': 2022, 'cited_by_count': 10}, {'year': 2021, 'cited_by_count': 16}, {'year': 2020, 'cited_by_count': 16}, {'year': 2019, 'cited_by_count': 13}, {'year': 2018, 'cited_by_count': 2}], 'updated_date': '2024-12-29T00:04:37.042405', 'created_date': '2018-05-17'}
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