Abstract
Histone Deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are at different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. Also, clinical trials of several HDAC inhibitors for use as anti-cancer drugs (alone or in combination with other anti-cancer therapeutics) are ongoing. In the intensifying efforts to discover new, hopefully, more therapeutically efficacious HDAC inhibitors, molecular modelingbased rational drug design has played an important role. In this review, we summarize four major structural classes of HDAC inhibitors (hydroxamic acid derivatives, aminobenzamide, cyclic peptide and short-chain fatty acids) that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.
Keywords: Histone deacetylase inhibitors (HDACis), epigenetic, histone deacetylases and cancer, HDACis as antitumor agents, natural HDACis, QSAR of HDACis, molecular modeling studies of HDACis.
[http://dx.doi.org/10.1038/nrc1779] [PMID: 16397526]
[http://dx.doi.org/10.1038/nrd2133] [PMID: 16955068]
[http://dx.doi.org/10.1016/j.canlet.2008.10.047] [PMID: 19103471]
[http://dx.doi.org/10.1073/pnas.1204429109] [PMID: 22493260]
[http://dx.doi.org/10.1038/icb.2011.100] [PMID: 22124371]
[http://dx.doi.org/10.1038/nrd4360] [PMID: 25131830]
[http://dx.doi.org/10.1158/1541-7786.MCR-07-0324] [PMID: 17951399]
[http://dx.doi.org/10.2174/092986708783885282] [PMID: 18336280]
[http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.095825] [PMID: 15822187]
[http://dx.doi.org/10.1002/ijc.22751] [PMID: 17455259]
[http://dx.doi.org/10.1124/mol.105.014167] [PMID: 15955865]
[http://dx.doi.org/10.1038/nbt1272] [PMID: 17211407]
[http://dx.doi.org/10.4155/fmc.12.3] [PMID: 22416777]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1786] [PMID: 18245542]
[http://dx.doi.org/10.1358/dof.2007.032.04.1094476]
[http://dx.doi.org/10.4103/abr.abr_142_19] [PMID: 31737580]
(b)Hrabeta, J.; Stiborova, M.; Adam, V.; Kizek, R.; Eckschlager, T. Histone deacetylase inhibitors in cancer therapy. A review. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2014, 158(2), 161-169.
[http://dx.doi.org/10.5507/bp.2013.085] [PMID: 24263215]
(c)Behera, J.; Jayaprakash, V.; Sinha, B.N. Histone deacetylase inhibitors: a review on class-I specific inhibition. Mini Rev. Med. Chem., 2015, 15(9), 731-750.
[http://dx.doi.org/10.2174/1389557515666150521162237] [PMID: 25994050]
[http://dx.doi.org/10.1042/bj20021321] [PMID: 12429021]
[http://dx.doi.org/10.1016/j.jmb.2004.02.006] [PMID: 15050820]
[http://dx.doi.org/10.1111/j.1574-6976.2007.00100.x] [PMID: 18221488]
[http://dx.doi.org/10.1128/MCB.25.8.2873-2884.2005] [PMID: 15798178]
[http://dx.doi.org/10.1139/o01-116] [PMID: 11467747]
[http://dx.doi.org/10.1038/nrm2346] [PMID: 18292778]
[http://dx.doi.org/10.1016/j.jss.2010.12.035] [PMID: 21392795]
[http://dx.doi.org/10.1038/ni.1673] [PMID: 19011628]
[http://dx.doi.org/10.1182/blood-2010-08-303701] [PMID: 21239696]
[http://dx.doi.org/10.1074/jbc.M809394200] [PMID: 19276081]
[http://dx.doi.org/10.1006/bbrc.2000.3000] [PMID: 10873683]
[http://dx.doi.org/10.1186/gb-2004-5-5-224] [PMID: 15128440]
(a)Yamamoto, H.; Schoonjans, K.; Auwerx, J. Sirtuin functions in health and disease. Mol. Endocrinol., 2007, 21(8), 1745-1755.
[http://dx.doi.org/10.1210/me.2007-0079] [PMID: 17456799]
[http://dx.doi.org/10.1006/bbrc.1999.0897] [PMID: 10381378]
[http://dx.doi.org/10.1042/BJ20070140] [PMID: 17447894]
[http://dx.doi.org/10.1016/j.molcel.2005.02.022] [PMID: 15780941]
[http://dx.doi.org/10.4155/fmc.14.44] [PMID: 24962284]
[http://dx.doi.org/10.1021/acs.jmedchem.5b00719] [PMID: 26299766]
[http://dx.doi.org/10.2174/0929867322666150821100720] [PMID: 26295463]
[http://dx.doi.org/10.3390/molecules191220295] [PMID: 25486244]
[http://dx.doi.org/10.2174/138161209787185742] [PMID: 19149606]
[http://dx.doi.org/10.1016/S1474-4422(11)70013-8] [PMID: 21349442]
[http://dx.doi.org/10.1038/nrm3293] [PMID: 22395773]
[http://dx.doi.org/10.1038/ng1531] [PMID: 15765097]
[http://dx.doi.org/10.1080/17460441.2020.1736032] [PMID: 32116055]
[http://dx.doi.org/10.1007/978-3-642-21631-2_3] [PMID: 21879445]
[http://dx.doi.org/10.1586/era.10.62] [PMID: 20553216]
[PMID: 21416059]
[http://dx.doi.org/10.1634/theoncologist.12-10-1247] [PMID: 17962618]
[http://dx.doi.org/10.1200/JCO.2008.21.6150] [PMID: 19826128]
[http://dx.doi.org/10.1200/JCO.2010.28.9066] [PMID: 20697094]
[http://dx.doi.org/10.1111/bjh.13222] [PMID: 25404094]
[http://dx.doi.org/10.7164/antibiotics.47.301] [PMID: 7513682]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-3119] [PMID: 25802282]
[PMID: 27668050]
[http://dx.doi.org/10.1016/S1470-2045(14)70440-1] [PMID: 25242045]
[http://dx.doi.org/10.1038/sj.bjc.6603463]
[http://dx.doi.org/10.2174/1568026619666190122144949] [PMID: 30674261]
[http://dx.doi.org/10.1007/s11060-014-1433-2] [PMID: 24728831]
[http://dx.doi.org/10.1371/journal.pone.0024468] [PMID: 21931726]
[PMID: 22263060]
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0933] [PMID: 23686769]
[http://dx.doi.org/10.1186/1748-717X-7-165] [PMID: 23017053]
[http://dx.doi.org/10.1111/bjh.12326] [PMID: 23590726]
[http://dx.doi.org/10.1007/s10147-011-0348-6] [PMID: 22234637]
[http://dx.doi.org/10.1016/bs.acr.2018.02.006] [PMID: 29551127]
[http://dx.doi.org/10.1038/sj.onc.1210204] [PMID: 17322921]
[http://dx.doi.org/10.1200/JCO.2009.22.1291] [PMID: 19826124]
[http://dx.doi.org/10.1038/sj.onc.1210620] [PMID: 17694093]
[http://dx.doi.org/10.1016/j.clml.2016.08.009] [PMID: 27637428]
[http://dx.doi.org/10.1080/10428194.2017.1361022] [PMID: 28853310]
[http://dx.doi.org/10.1016/j.bioorg.2016.05.005] [PMID: 27239721]
[http://dx.doi.org/10.1021/ja9613724]
[http://dx.doi.org/10.1006/excr.1998.4027] [PMID: 9633520]
[http://dx.doi.org/10.7164/antibiotics.47.311] [PMID: 8175483]
[http://dx.doi.org/10.7164/antibiotics.47.315] [PMID: 8175484]
[http://dx.doi.org/10.1182/blood-2010-10-312603] [PMID: 21355097]
[http://dx.doi.org/10.1016/j.biopha.2014.01.002] [PMID: 24485799]
[PMID: 24416998]
[http://dx.doi.org/10.3109/07357907.2012.675382] [PMID: 22536933]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0095] [PMID: 23757352]
[http://dx.doi.org/10.1200/jco.2013.31.15_suppl.tps8616]
[http://dx.doi.org/10.1007/s40265-014-0275-8] [PMID: 25134672]
[http://dx.doi.org/10.1200/JCO.2010.32.4467] [PMID: 21502553]
[http://dx.doi.org/10.1016/j.ejca.2010.02.047] [PMID: 20304628]
[http://dx.doi.org/10.1016/j.ygyno.2012.02.019] [PMID: 22366594]
[http://dx.doi.org/10.1007/s00262-020-02537-4]
[http://dx.doi.org/10.3109/10428194.2013.877134] [PMID: 24369094]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0968] [PMID: 25189481]
[http://dx.doi.org/10.1007/s10637-009-9219-7] [PMID: 19172229]
[http://dx.doi.org/10.1097/CAD.0000000000000122] [PMID: 24800886]
[http://dx.doi.org/10.1038/nbt.1724] [PMID: 21139608]
[http://dx.doi.org/10.1016/j.ejca.2012.08.017] [PMID: 22981498]
[http://dx.doi.org/10.1007/s10637-011-9666-9] [PMID: 21484248]
[http://dx.doi.org/10.1200/JCO.2011.38.1350] [PMID: 22547596]
[http://dx.doi.org/10.1038/leu.2013.325] [PMID: 24186004]
[http://dx.doi.org/10.1002/ajh.22198] [PMID: 22072492]
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0530] [PMID: 26362997]
[http://dx.doi.org/10.1038/43710] [PMID: 10490031]
[http://dx.doi.org/10.1016/0378-1119(95)00214-Q] [PMID: 7628704]
[http://dx.doi.org/10.2174/0929867043365099] [PMID: 15180568]
[http://dx.doi.org/10.1006/excr.1994.1248] [PMID: 8082721]
[http://dx.doi.org/10.1016/S0168-8278(01)00257-4] [PMID: 11830335]
[PMID: 12479699]
[http://dx.doi.org/10.1002/mc.10145] [PMID: 14502645]
[http://dx.doi.org/10.3892/ijo.22.5.1129] [PMID: 12684681]
[http://dx.doi.org/10.1677/joe.0.1790041] [PMID: 14529564]
[http://dx.doi.org/10.1200/JCO.2005.14.167] [PMID: 15897550]
[http://dx.doi.org/10.1200/JCO.2005.01.9679] [PMID: 16330674]
[PMID: 14506144]
[http://dx.doi.org/10.1182/blood-2006-06-025999] [PMID: 16960145]
[PMID: 19417023]
[http://dx.doi.org/10.1007/s10637-015-0206-x] [PMID: 25600050]
[http://dx.doi.org/10.3324/haematol.2016.154377] [PMID: 28126962]
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0624]
[http://dx.doi.org/10.1080/1120009X.2016.1145375] [PMID: 27121910]
[http://dx.doi.org/10.1111/j.1365-2141.2010.08266.x] [PMID: 20560970]
[http://dx.doi.org/10.2119/molmed.2011.00020] [PMID: 21365126]
[http://dx.doi.org/10.1111/bjh.12332] [PMID: 23573950]
[http://dx.doi.org/10.1021/jm301098e] [PMID: 23009203]
[http://dx.doi.org/10.1038/bcj.2012.14] [PMID: 22829971]
[http://dx.doi.org/10.1002/cncr.30533] [PMID: 28094841]
[http://dx.doi.org/10.1002/pbc.24694] [PMID: 23893953]
[http://dx.doi.org/10.1111/j.1365-2141.2010.08124.x] [PMID: 20201941]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0735] [PMID: 24065624]
[http://dx.doi.org/10.1182/blood.V116.21.2811.2811]
[http://dx.doi.org/10.1182/blood.V118.21.2675.2675]
[http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e15088]
[http://dx.doi.org/10.1021/jm901453q] [PMID: 20143778]
[http://dx.doi.org/10.1158/0008-5472.CAN-09-3360] [PMID: 20388807]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0220] [PMID: 25239935]
[http://dx.doi.org/10.1182/blood.V124.21.3124.3124]
[http://dx.doi.org/10.1093/neuonc/nor072] [PMID: 21778190]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0203] [PMID: 18483287]
[http://dx.doi.org/10.1021/jm0503749] [PMID: 16107152]
[http://dx.doi.org/10.1111/j.1365-2141.2010.08126.x] [PMID: 20331455]
[http://dx.doi.org/10.1002/pbc.24724] [PMID: 24038993]
[http://dx.doi.org/10.1021/ja102758v] [PMID: 20614936]
[http://dx.doi.org/10.1073/pnas.1013754107] [PMID: 21037108]
[http://dx.doi.org/10.1172/JCI80713] [PMID: 26524593]
[http://dx.doi.org/10.3109/10428194.2011.570821] [PMID: 21699378]
[http://dx.doi.org/10.3389/fneur.2015.00044] [PMID: 25798128]
[PMID: 11389076]
[http://dx.doi.org/10.1159/000292362] [PMID: 20215787]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0836] [PMID: 16061681]
[http://dx.doi.org/10.1016/j.bbamcr.2007.05.002] [PMID: 17555830]
[PMID: 14578462]
[http://dx.doi.org/10.3892/ijo.2011.943] [PMID: 21318222]
[http://dx.doi.org/10.1021/jm048944c] [PMID: 16033277]
[http://dx.doi.org/10.1135/cccc20061088]
(b)Cappellacci, L.; Franchetti, P.; Vita, P.; Petrelli, R.; Lavecchia, A.; Jayaram, H.N.; Saiko, P.; Graser, G.; Szekeres, T.; Grifantini, M. Ribose-modified purine nucleosides as ribonucleotide reductase inhibitors. Synthesis, antitumor activity, and molecular modeling of N6-substituted 3′-C-methyladenosine derivatives. J. Med. Chem., 2008, 51(14), 4260-4269.
[http://dx.doi.org/10.1021/jm800205c] [PMID: 18588281]
(c)Cappellacci, L.; Petrelli, R.; Franchetti, P.; Vita, P.; Kusumanchi, P.; Kumar, M.; Jayaram, H.N.; Zhou, B.; Yen, Y.; Grifantini, M. Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3′-C-methyl-ribonucleosides as antitumor agents. Eur. J. Med. Chem., 2011, 46(5), 1499-1504.
[http://dx.doi.org/10.1016/j.ejmech.2011.01.055] [PMID: 21349610]
[http://dx.doi.org/10.2174/1573406053765431]
[http://dx.doi.org/10.18632/oncotarget.430] [PMID: 22289787]
[http://dx.doi.org/10.1111/j.1349-7006.2011.01921.x] [PMID: 21375679]
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3165] [PMID: 22553374]
[http://dx.doi.org/10.1007/s00280-012-1847-5] [PMID: 22362161]
[http://dx.doi.org/10.2147/OTT.S93528] [PMID: 28138258]
[http://dx.doi.org/10.1073/pnas.96.8.4592] [PMID: 10200307]
[http://dx.doi.org/10.1038/bjc.2011.527] [PMID: 22134508]
[http://dx.doi.org/10.1186/1756-8722-3-5] [PMID: 20132536]
[PMID: 12839953]
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2026] [PMID: 18413790]
[http://dx.doi.org/10.1182/blood-2007-10-115873] [PMID: 18495956]
[http://dx.doi.org/10.1111/j.1365-2141.2009.07881.x] [PMID: 19747365]
[http://dx.doi.org/10.1016/S1470-2045(11)70265-0] [PMID: 22033282]
[http://dx.doi.org/10.1023/A:1006489328324] [PMID: 11291827]
[http://dx.doi.org/10.1038/leu.2013.231] [PMID: 23913134]
[http://dx.doi.org/10.7164/antibiotics.56.72] [PMID: 12715864]
[http://dx.doi.org/10.1038/ja.2010.51] [PMID: 20588300]
[http://dx.doi.org/10.1002/cmdc.200700095] [PMID: 17694590]
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0738] [PMID: 21115653]
[http://dx.doi.org/10.1634/theoncologist.2011-0031] [PMID: 21632454]
[http://dx.doi.org/10.1007/s00280-014-2384-1] [PMID: 24435060]
[PMID: 25202113]
[http://dx.doi.org/10.1590/S1415-475738420150028] [PMID: 26692161]
[http://dx.doi.org/10.1016/j.bmcl.2014.09.046] [PMID: 25304896]
[http://dx.doi.org/10.2165/11591280-000000000-00000] [PMID: 21902286]
[http://dx.doi.org/10.1196/annals.1378.080] [PMID: 17341628]
[PMID: 11595694]
[PMID: 10690554]
[http://dx.doi.org/10.1007/s00280-001-0390-6] [PMID: 11855750]
[PMID: 2211619]
[http://dx.doi.org/10.1038/nchembio.1223] [PMID: 23524983]
[http://dx.doi.org/10.3892/ijo.2016.3402] [PMID: 26936390]
[http://dx.doi.org/10.1002/cam4.939] [PMID: 27981793]
[http://dx.doi.org/10.1124/jpet.102.042903] [PMID: 12538846]
[http://dx.doi.org/10.1074/jbc.M106699200] [PMID: 11698395]
[http://dx.doi.org/10.1002/anie.200602047] [PMID: 16981208]
[http://dx.doi.org/10.1021/jm4008449] [PMID: 23865683]
[http://dx.doi.org/10.1073/pnas.98.1.87] [PMID: 11134513]
[http://dx.doi.org/10.1016/j.ejca.2008.01.023] [PMID: 18295477]
[http://dx.doi.org/10.1021/ja7110064] [PMID: 18205365]
[http://dx.doi.org/10.1016/j.cbi.2014.07.004] [PMID: 25078973]
[http://dx.doi.org/10.1016/j.jss.2014.02.042] [PMID: 24679699]
[http://dx.doi.org/10.1016/0196-9781(93)90160-I] [PMID: 8134289]
[http://dx.doi.org/10.1021/acs.jmedchem.5b01632] [PMID: 26681404]
[http://dx.doi.org/10.1021/ol070382e] [PMID: 17397173]
[http://dx.doi.org/10.1371/journal.pone.0073097] [PMID: 24023672]
[http://dx.doi.org/10.1530/ERC-13-0171] [PMID: 24500760]
[http://dx.doi.org/10.1089/ars.2014.6097] [PMID: 25364882]
[PMID: 14522905]
[http://dx.doi.org/10.1155/2011/135039] [PMID: 21317983]
[http://dx.doi.org/10.1038/nrd2137] [PMID: 19794444]
[http://dx.doi.org/10.2217/fon.13.108] [PMID: 23902242]
[http://dx.doi.org/10.1016/j.canlet.2017.03.020] [PMID: 28323035]
[http://dx.doi.org/10.1158/1940-6207.CAPR-16-0044] [PMID: 27138790]
[PMID: 16475702]
[http://dx.doi.org/10.1111/j.1745-7270.2007.00356.x] [PMID: 17989874]
[http://dx.doi.org/10.3892/or.19.1.275] [PMID: 18097607]
[http://dx.doi.org/10.1080/01635581.2012.721156] [PMID: 23163853]
[http://dx.doi.org/10.1016/S0960-894X(02)00754-0] [PMID: 12419380]
[http://dx.doi.org/10.1016/j.bmcl.2004.08.016] [PMID: 15454224]
[http://dx.doi.org/10.1002/cmdc.201300433] [PMID: 24375963]
[PMID: 17201152]
[http://dx.doi.org/10.2174/138945012802008973] [PMID: 22594471]
[http://dx.doi.org/10.1073/pnas.95.7.3356] [PMID: 9520369]
[PMID: 8226751]
[http://dx.doi.org/10.1021/np500387h] [PMID: 24999749]
[http://dx.doi.org/10.1039/c2np00066k] [PMID: 22334030]
[http://dx.doi.org/10.1021/ml500170r] [PMID: 25147612]
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2347] [PMID: 18483295]
[http://dx.doi.org/10.1016/j.bmcl.2008.10.029] [PMID: 18954983]
[http://dx.doi.org/10.3762/bjoc.9.11] [PMID: 23400330]
[http://dx.doi.org/10.1021/jm0303094] [PMID: 14613312]
[http://dx.doi.org/10.1080/14756366.2017.1417274] [PMID: 29616828]
[http://dx.doi.org/10.1016/j.bmcl.2010.03.091] [PMID: 20392638]
[http://dx.doi.org/10.1074/jbc.M113.490706] [PMID: 23897821]
[PMID: 25587304]
[http://dx.doi.org/10.2174/138161208783885335] [PMID: 18336298]
[http://dx.doi.org/10.1248/cpb.57.897] [PMID: 19721249]
[http://dx.doi.org/10.1002/cmdc.201300413] [PMID: 24730063]
[http://dx.doi.org/10.4155/fmc.13.141] [PMID: 24024943]
[http://dx.doi.org/10.2174/1568026616666160212122609] [PMID: 26873193]
[http://dx.doi.org/10.2174/1389450118666170112130151] [PMID: 28078985]
[http://dx.doi.org/10.1042/BJ20070779] [PMID: 17868033]
[http://dx.doi.org/10.2174/1568026615666150813145629] [PMID: 26268343]
[http://dx.doi.org/10.1039/b703830p] [PMID: 18568166]
[http://dx.doi.org/10.1016/j.canlet.2009.02.013] [PMID: 19289255]
[http://dx.doi.org/10.1021/acs.jmedchem.5b00229] [PMID: 26086931]
[http://dx.doi.org/10.1021/jm401053m] [PMID: 24074025]
[http://dx.doi.org/10.1002/cmdc.201500293] [PMID: 26412596]
[http://dx.doi.org/10.1021/jm301355j] [PMID: 23368884]
[http://dx.doi.org/10.1021/jm400385r] [PMID: 23964961]
[http://dx.doi.org/10.1021/jm400390r] [PMID: 23672185]
[http://dx.doi.org/10.1021/jm301254q] [PMID: 23252603]
[http://dx.doi.org/10.1021/acsmedchemlett.5b00302] [PMID: 26819662]
[http://dx.doi.org/10.1021/jm4011884] [PMID: 24261862]
[http://dx.doi.org/10.1007/s00018-014-1656-6] [PMID: 24898083]
[http://dx.doi.org/10.3390/molecules20033898] [PMID: 25738536]
[http://dx.doi.org/10.1016/j.bmc.2010.06.081] [PMID: 20650640]
[http://dx.doi.org/10.1016/S0092-8674(02)00625-6] [PMID: 11832206]
[http://dx.doi.org/10.1172/JCI69738] [PMID: 24382387]
[PMID: 12481415]
[PMID: 23836985]
[PMID: 15078986]
[http://dx.doi.org/10.1371/journal.pone.0053766] [PMID: 23320102]
[http://dx.doi.org/10.1038/86507] [PMID: 11283670]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4598] [PMID: 16951198]
[http://dx.doi.org/10.1073/pnas.1008522107] [PMID: 20679231]
[http://dx.doi.org/10.1517/14728222.9.4.809] [PMID: 16083344]
[http://dx.doi.org/10.1016/j.semcancer.2006.09.005] [PMID: 17095247]
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2088] [PMID: 16000590]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3996] [PMID: 17545612]
[http://dx.doi.org/10.1073/pnas.0707828104] [PMID: 18042714]
[http://dx.doi.org/10.5012/bkcs.2012.33.6.2063]
[http://dx.doi.org/10.1016/j.bmcl.2010.12.079] [PMID: 21256006]
[http://dx.doi.org/10.1016/j.bmcl.2012.04.045] [PMID: 22578459]
[http://dx.doi.org/10.1002/med.20200] [PMID: 20162725]
[http://dx.doi.org/10.1021/jm401225q] [PMID: 24304348]
[http://dx.doi.org/10.1016/j.bmc.2008.03.050] [PMID: 18397827]
[http://dx.doi.org/10.1016/j.bmc.2008.08.003] [PMID: 18715788]
[http://dx.doi.org/10.1002/cmdc.201300372] [PMID: 24285590]
[http://dx.doi.org/10.1021/jm2001025] [PMID: 21548582]
[http://dx.doi.org/10.2174/1386207319666160801154415] [PMID: 27487787]
[http://dx.doi.org/10.1080/07391102.2012.10507409] [PMID: 22208272]
[http://dx.doi.org/10.1371/journal.pone.0049327] [PMID: 23209570]
[http://dx.doi.org/10.1007/s00894-011-1240-z] [PMID: 21968575]
[http://dx.doi.org/10.1016/j.bmc.2010.03.080] [PMID: 20472442]
[http://dx.doi.org/10.1002/jcc.23390] [PMID: 23893931]
[http://dx.doi.org/10.1016/j.apsb.2011.10.002]
[http://dx.doi.org/10.1002/cmdc.201100007] [PMID: 21416613]
[http://dx.doi.org/10.1007/s00044-010-9519-7]
[http://dx.doi.org/10.1002/cmdc.200900500] [PMID: 20157916]
[http://dx.doi.org/10.1371/journal.ppat.1003645] [PMID: 24086136]
[http://dx.doi.org/10.1021/ml300322n] [PMID: 23526571]
[http://dx.doi.org/10.1021/jm500724x] [PMID: 25007006]
[http://dx.doi.org/10.1016/j.bbapap.2012.08.009] [PMID: 23457710]
[http://dx.doi.org/10.1080/07391102.2013.879073] [PMID: 24460542]
[http://dx.doi.org/10.1016/j.jmgm.2010.07.007] [PMID: 20870437]
[http://dx.doi.org/10.1186/1756-8722-2-31] [PMID: 19635146]
[http://dx.doi.org/10.1038/sj.bjc.6605293] [PMID: 19738609]
[http://dx.doi.org/10.1200/JCO.2006.08.6165] [PMID: 17513804]
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0985] [PMID: 19372552]
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0038] [PMID: 19509253]
[http://dx.doi.org/10.3892/ijo.2015.2996] [PMID: 25963435]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0122] [PMID: 18981013]
[http://dx.doi.org/10.1007/s10549-006-9459-6] [PMID: 17186358]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2478] [PMID: 15867379]
[http://dx.doi.org/10.2217/fon.11.2] [PMID: 21345145]
[http://dx.doi.org/10.1007/s00280-010-1289-x] [PMID: 20217089]
[http://dx.doi.org/10.1093/annonc/mdp270] [PMID: 19608618]
[http://dx.doi.org/10.1002/pros.21187] [PMID: 20687225]
[http://dx.doi.org/10.1038/sj.bjc.6605726] [PMID: 20588278]
[http://dx.doi.org/10.1038/nrc2607] [PMID: 19377506]
[http://dx.doi.org/10.1021/cr900097c] [PMID: 19476377]
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0254] [PMID: 19887547]
[http://dx.doi.org/10.1007/s11060-010-0127-7] [PMID: 20135194]
[http://dx.doi.org/10.1007/s10637-010-9467-6] [PMID: 20533074]
[http://dx.doi.org/10.1007/s00428-006-0173-x] [PMID: 16568310]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1931] [PMID: 19318485]
[http://dx.doi.org/10.1101/gad.947102] [PMID: 11782440]
[http://dx.doi.org/10.1002/cncr.21792] [PMID: 16532500]
[http://dx.doi.org/10.1200/JCO.2002.04.117] [PMID: 12011120]
[http://dx.doi.org/10.1002/ajh.23464] [PMID: 23619977]
[http://dx.doi.org/10.1053/j.seminhematol.2007.11.007] [PMID: 18179966]
[http://dx.doi.org/10.1038/5047] [PMID: 9916800]
[PMID: 12738711]
[http://dx.doi.org/10.1371/journal.pone.0000098] [PMID: 17183730]
[http://dx.doi.org/10.1093/annonc/mdm204] [PMID: 17761710]
[http://dx.doi.org/10.1002/cncr.22087] [PMID: 16888795]
[http://dx.doi.org/10.1111/j.1365-2559.2010.03494.x] [PMID: 20459566]
[http://dx.doi.org/10.1159/000279388] [PMID: 20130423]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4397] [PMID: 17409421]
[http://dx.doi.org/10.1074/jbc.M500403200] [PMID: 15713663]
[http://dx.doi.org/10.2174/187152061405140501101624] [PMID: 23140355]
[http://dx.doi.org/10.1200/JCO.2015.63.4154] [PMID: 27022112]
[http://dx.doi.org/10.3390/ph3092751] [PMID: 27713375]
[http://dx.doi.org/10.1093/annonc/mdn703] [PMID: 19150934]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1988] [PMID: 16424029]
[http://dx.doi.org/10.3748/wjg.v13.i33.4458] [PMID: 17724801]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0469] [PMID: 18765530]
[http://dx.doi.org/10.1182/blood-2010-11-318055] [PMID: 21292776]
[http://dx.doi.org/10.1007/s00277-009-0793-8] [PMID: 19633847]
[http://dx.doi.org/10.1002/cmdc.201500486] [PMID: 26603496]