跳转到内容

抗靶标

维基百科,自由的百科全书

在药物学中,一个抗靶标可以是一个受体,或者其它生物靶标,当其和药物作用时会引起不希望的不良反应副反应)。对于药物研发公司来说,在药物设计和开发过程中确保新药不和大量的被意外发现的抗靶标产生显著活性是至关重要的。[1][2]


最知名和最显著的抗靶标分别是hERG通道和5-HT2B 受体,会在小范围但不可预知比例的用药人身上分别引发心脏功能的长期问题——QT间期延长综合症心肌纤维化。这些靶标的发现是由于某些上市药物高频率的特有不良反应;一些具有显著hERG活性的老药依然被警示使用中,大部分被发现是强烈的 5-HT2B激动剂的药物不得不从市场退市。因此,任何先导化合物如果在初期的药物筛选中显示出和这些靶标有较高的亲和力,几乎都会被终止开发。 [3][4][5][6][7][8]

参考文献

[编辑]
  1. ^ Thomas Klabunde, Andreas Evers. GPCR antitarget modeling: pharmacophore models for biogenic amine binding GPCRs to avoid GPCR-mediated side effects. Chembiochem: A European Journal of Chemical Biology. 2005-05, 6 (5): 876–889 [2019-02-12]. ISSN 1439-4227. PMID 15791686. doi:10.1002/cbic.200400369. (原始内容存档于2016-06-10). 
  2. ^ David A. Price, Julian Blagg, Lyn Jones, Nigel Greene, Travis Wager. Physicochemical drug properties associated with in vivo toxicological outcomes: a review. Expert Opinion on Drug Metabolism & Toxicology. 2009-08, 5 (8): 921–931 [2019-02-12]. ISSN 1744-7607. PMID 19519283. doi:10.1517/17425250903042318. (原始内容存档于2014-11-03). 
  3. ^ Fabrizio De Ponti, Elisabetta Poluzzi, Andrea Cavalli, Maurizio Recanatini, Nicola Montanaro. Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade de pointes: an overview. Drug Safety. 2002, 25 (4): 263–286 [2019-02-12]. ISSN 0114-5916. PMID 11994029. doi:10.2165/00002018-200225040-00004. (原始内容存档于2015-01-02). 
  4. ^ Maurizio Recanatini, Elisabetta Poluzzi, Matteo Masetti, Andrea Cavalli, Fabrizio De Ponti. QT prolongation through hERG K(+) channel blockade: current knowledge and strategies for the early prediction during drug development. Medicinal Research Reviews. 2005-03, 25 (2): 133–166 [2019-02-12]. ISSN 0198-6325. PMID 15389727. doi:10.1002/med.20019. (原始内容存档于2015-11-28). 
  5. ^ Emanuel Raschi, Valentina Vasina, Elisabetta Poluzzi, Fabrizio De Ponti. The hERG K+ channel: target and antitarget strategies in drug development. Pharmacological Research. 2008-03, 57 (3): 181–195 [2019-02-12]. ISSN 1043-6618. PMID 18329284. doi:10.1016/j.phrs.2008.01.009. (原始内容存档于2014-11-03). 
  6. ^ Emanuel Raschi, Luisa Ceccarini, Fabrizio De Ponti, Maurizio Recanatini. hERG-related drug toxicity and models for predicting hERG liability and QT prolongation. Expert Opinion on Drug Metabolism & Toxicology. 2009-09, 5 (9): 1005–1021 [2019-02-12]. ISSN 1744-7607. PMID 19572824. doi:10.1517/17425250903055070. (原始内容存档于2014-11-03). 
  7. ^ Xi-Ping Huang, Vincent Setola, Prem N. Yadav, John A. Allen, Sarah C. Rogan, Bonnie J. Hanson, Chetana Revankar, Matt Robers, Chris Doucette, Bryan L. Roth. Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment. Molecular Pharmacology. 2009-10, 76 (4): 710–722 [2019-02-12]. ISSN 1521-0111. PMC 2769050可免费查阅. PMID 19570945. doi:10.1124/mol.109.058057. (原始内容存档于2017-07-12). 
  8. ^ Sanjeev Bhattacharyya, Anthony H. Schapira, Dimitri P. Mikhailidis, Joseph Davar. Drug-induced fibrotic valvular heart disease. Lancet (London, England). 2009-08-15, 374 (9689): 577–585 [2019-02-12]. ISSN 1474-547X. PMID 19683643. doi:10.1016/S0140-6736(09)60252-X. (原始内容存档于2015-09-19).