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摘要
组蛋白去乙酰化酶(HDACs)是通过催化组蛋白去乙酰化维持体内平衡所必需的。HDACs的异常表达与多种人类疾病相关。尽管HDAC抑制剂在临床中被作为有效的化疗药物,但由于弱亚型选择性引起的相关副作用,其应用仍受到限制。HDAC1具有独特的结构和细胞定位以及多种底物,比其他亚型具有更广泛的生物学功能。HDAC1显示出一种独特的结构,主要在细胞核中发现,并参与表观遗传和转录调控。HDAC1广泛表达,并与Sin3、NuRD和CoRest转录抑制复合体相关,负责不同的细胞过程,如细胞增殖和存活。HDAC1抑制剂已被有效用于治疗各种癌症,如胃癌、乳腺癌、大肠癌、前列腺癌、结肠癌、肺癌、卵巢癌、胰腺癌和炎症,而不产生明显的毒性作用。本文综述了HDAC1抑制剂的四种主要结构类(羟肟酸衍生物、苯甲酰胺类、肼类和硫醇类)及其结构活性关系。本文综述了HDAC1抑制剂的研究进展,旨在深入了解HDAC1抑制剂的结构信息。这为开发新的选择性HDAC1抑制剂作为抗癌药物提供了最新的方向。
关键词: 组蛋白去乙酰化酶1(HDAC1),抗癌,羟肟酸衍生物,苯酰胺,肼,硫醇。
[http://dx.doi.org/10.1158/1055-9965.EPI-15-0578] [PMID: 26667886]
[http://dx.doi.org/10.1016/0955-0674(90)90021-6] [PMID: 2114126]
[http://dx.doi.org/10.1038/s41419-021-03488-z] [PMID: 33608500]
[http://dx.doi.org/10.1016/j.clinthera.2016.03.026] [PMID: 27158009]
[http://dx.doi.org/10.1038/s41417-020-00272-7] [PMID: 33432087]
[http://dx.doi.org/10.1016/j.bbcan.2021.188585] [PMID: 34224836]
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[http://dx.doi.org/10.1016/j.tranon.2021.101174] [PMID: 34243011]
[http://dx.doi.org/10.1016/j.bbcan.2021.188565] [PMID: 33992723]
[http://dx.doi.org/10.1038/s41467-021-21026-5] [PMID: 33536423]
[http://dx.doi.org/10.1016/S1470-2045(15)00077-7] [PMID: 26149886]
[http://dx.doi.org/10.1615/CritRevOncog.2015012997] [PMID: 25746103]
[http://dx.doi.org/10.1155/2016/8797206] [PMID: 27556043]
[http://dx.doi.org/10.1016/j.lfs.2021.119504] [PMID: 33872660]
[http://dx.doi.org/10.1042/bj20021321] [PMID: 12429021]
[http://dx.doi.org/10.1006/excr.2000.5080] [PMID: 11139331]
[http://dx.doi.org/10.1074/jbc.M510023200] [PMID: 16533812]
[http://dx.doi.org/10.1007/s12029-011-9257-1] [PMID: 21271301]
[http://dx.doi.org/10.1186/s12943-019-1127-7] [PMID: 31910827]
[http://dx.doi.org/10.1038/icb.2011.100] [PMID: 22124371]
[http://dx.doi.org/10.1155/2011/129383] [PMID: 21049000]
[http://dx.doi.org/10.1016/j.gene.2005.09.010] [PMID: 16289629]
[http://dx.doi.org/10.1038/cti.2015.46] [PMID: 26900475]
[http://dx.doi.org/10.1016/j.imbio.2006.05.007] [PMID: 16920490]
[http://dx.doi.org/10.1016/j.it.2011.04.001] [PMID: 21570914]
[http://dx.doi.org/10.1042/BJ20150517] [PMID: 26205489]
[http://dx.doi.org/10.1074/jbc.M000202200] [PMID: 10777477]
[http://dx.doi.org/10.1074/jbc.M507553200] [PMID: 16204234]
[http://dx.doi.org/10.1016/j.molcel.2013.05.020] [PMID: 23791785]
[http://dx.doi.org/10.2174/1573409914666180502113135] [PMID: 29732991]
[http://dx.doi.org/10.1080/07391102.2018.1441072] [PMID: 29447615]
[http://dx.doi.org/10.1093/emboj/20.7.1739] [PMID: 11285237]
[http://dx.doi.org/10.1586/era.10.88] [PMID: 20645688]
[http://dx.doi.org/10.3390/ijms18071414] [PMID: 28671573]
[http://dx.doi.org/10.2174/09298673113209990191] [PMID: 23895688]
[http://dx.doi.org/10.1021/jm020377a] [PMID: 12593661]
[http://dx.doi.org/10.1021/jm0605536] [PMID: 17004718]
[http://dx.doi.org/10.1021/jm0703136] [PMID: 17691763]
[http://dx.doi.org/10.1021/jm100007m] [PMID: 20205394]
[http://dx.doi.org/10.1016/j.bmcl.2011.08.022] [PMID: 21875796]
[http://dx.doi.org/10.1016/j.bmcl.2014.06.080] [PMID: 25182565]
[http://dx.doi.org/10.1016/j.bmcl.2007.05.091] [PMID: 17576064]
[http://dx.doi.org/10.1021/jm2003552] [PMID: 21634430]
[http://dx.doi.org/10.1016/j.bmcl.2009.01.041] [PMID: 19181524]
[http://dx.doi.org/10.1016/j.bmcl.2011.06.015] [PMID: 21742496]
[http://dx.doi.org/10.1021/jm020154k] [PMID: 12061890]
[http://dx.doi.org/10.1039/C5OB02250A] [PMID: 26732459]
[http://dx.doi.org/10.1016/j.bmcl.2018.11.027] [PMID: 30455152]
[http://dx.doi.org/10.3390/molecules24142569] [PMID: 31311163]
[http://dx.doi.org/10.1021/jm011088+] [PMID: 11960489]
[http://dx.doi.org/10.1021/jm031036f] [PMID: 14998325]
[http://dx.doi.org/10.1021/jm8005355] [PMID: 19007204]
[http://dx.doi.org/10.1016/j.bmcl.2013.03.102] [PMID: 23601706]
[http://dx.doi.org/10.1016/j.bmcl.2010.04.041] [PMID: 20451378]
[http://dx.doi.org/10.1021/jm061082q] [PMID: 17419603]
[http://dx.doi.org/10.1021/jm801128g] [PMID: 19093884]
[http://dx.doi.org/10.1038/s41598-020-67112-4] [PMID: 32591593]
[http://dx.doi.org/10.1016/j.bmc.2004.01.014] [PMID: 15018907]
[http://dx.doi.org/10.1016/j.bmc.2013.03.049] [PMID: 23602523]
[http://dx.doi.org/10.1021/jm901667k] [PMID: 20055418]
[http://dx.doi.org/10.1016/j.bmc.2013.09.023] [PMID: 24095018]
[http://dx.doi.org/10.1021/ml100295v] [PMID: 21572592]
[http://dx.doi.org/10.1016/j.bmc.2019.07.055] [PMID: 31420257]
[http://dx.doi.org/10.1016/j.bmcl.2013.03.084] [PMID: 23591111]
[http://dx.doi.org/10.1021/ml400470s] [PMID: 24944733]
[http://dx.doi.org/10.1016/j.bmc.2014.08.030] [PMID: 25261927]
[http://dx.doi.org/10.1016/j.ejmech.2017.01.035] [PMID: 28213282]
[http://dx.doi.org/10.1016/j.bmc.2016.12.001] [PMID: 28336407]
[http://dx.doi.org/10.2147/DDDT.S237957] [PMID: 32103894]
[http://dx.doi.org/10.1016/j.ejmech.2020.112189] [PMID: 32151834]
[http://dx.doi.org/10.1021/jm100507q] [PMID: 20669972]
[http://dx.doi.org/10.1016/j.ejmech.2013.05.017] [PMID: 23792316]
[http://dx.doi.org/10.1039/C8MD00454D] [PMID: 31391882]
[http://dx.doi.org/10.1111/cbdd.13405] [PMID: 30251407]
[http://dx.doi.org/10.1021/jm101605z] [PMID: 21476600]
[http://dx.doi.org/10.1021/jm400179b] [PMID: 23570542]
[http://dx.doi.org/10.1016/j.bmc.2008.07.066] [PMID: 18701301]
[http://dx.doi.org/10.1016/j.bmcl.2007.06.038] [PMID: 17588744]
[http://dx.doi.org/10.1016/j.bmc.2006.07.008] [PMID: 16877001]
[http://dx.doi.org/10.1016/j.bmc.2014.06.031] [PMID: 25022972]
[http://dx.doi.org/10.1016/j.bmcl.2010.12.079] [PMID: 21256006]
[http://dx.doi.org/10.1021/ml1001954] [PMID: 21874153]
[http://dx.doi.org/10.1016/j.ejmech.2011.06.002] [PMID: 21712146]
[http://dx.doi.org/10.1016/j.bmc.2011.11.041] [PMID: 22182579]
[http://dx.doi.org/10.1021/ml300366t] [PMID: 23493449]
[http://dx.doi.org/10.1016/j.bmc.2014.05.001] [PMID: 24864038]
[http://dx.doi.org/10.1016/j.bmc.2019.03.008] [PMID: 30879863]
[http://dx.doi.org/10.1021/acs.jmedchem.7b00197] [PMID: 28574690]
[http://dx.doi.org/10.1016/j.bmcl.2007.12.009] [PMID: 18160287]
[http://dx.doi.org/10.1016/j.bmcl.2007.10.050] [PMID: 17977726]
[http://dx.doi.org/10.1016/j.ejmech.2015.05.045] [PMID: 26140961]
[http://dx.doi.org/10.1016/j.ejmech.2017.03.024] [PMID: 28340413]
[http://dx.doi.org/10.1016/j.bmcl.2006.05.005] [PMID: 16713259]
[http://dx.doi.org/10.1016/j.ejmech.2012.03.058] [PMID: 22541394]
[http://dx.doi.org/10.1016/j.ejmech.2018.10.066] [PMID: 30476825]
[http://dx.doi.org/10.1016/j.ejmech.2019.02.032] [PMID: 30802729]
[http://dx.doi.org/10.1021/acs.jmedchem.1c01472] [PMID: 34942071]
[http://dx.doi.org/10.1080/14756366.2020.1870457] [PMID: 33445997]
[http://dx.doi.org/10.1016/j.chembiol.2014.12.015] [PMID: 25699604]
[http://dx.doi.org/10.1021/acs.jmedchem.6b01385] [PMID: 27754681]
[http://dx.doi.org/10.1021/acs.jmedchem.8b00136] [PMID: 29499113]
[http://dx.doi.org/10.1021/ja8033763] [PMID: 18642817]
[http://dx.doi.org/10.1021/jm5008209] [PMID: 25233084]
[http://dx.doi.org/10.1016/j.bmc.2017.03.071] [PMID: 28416100]
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