抗靶標

在藥物學中，一個抗靶標可以是一個受體，酶，或者其它生物靶標，當其和藥物作用時會引起不希望的不良反應（副反應）。對於藥物研發公司來說，在藥物設計和開發過程中確保新藥不和大量的被意外發現的抗靶標產生顯著活性是至關重要的。^[1]^[2]

最知名和最顯著的抗靶標分別是hERG通道和5-HT_2B 受體，會在小範圍但不可預知比例的用藥人身上分別引發心臟功能的長期問題——QT間期延長綜合症和心肌纖維化。這些靶標的發現是由於某些上市藥物高頻率的特有不良反應；一些具有顯著hERG活性的老藥依然被警示使用中，大部分被發現是強烈的 5-HT_2B激動劑的藥物不得不從市場退市。因此，任何先導化合物如果在初期的藥物篩選中顯示出和這些靶標有較高的親和力，幾乎都會被終止開發。 ^[3]^[4]^[5]^[6]^[7]^[8]

參考文獻[編輯]

^ 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. （原始內容存檔於2016-06-10）.
^ 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. （原始內容存檔於2014-11-03）.
^ 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. （原始內容存檔於2015-01-02）.
^ 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. （原始內容存檔於2015-11-28）.
^ 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. （原始內容存檔於2014-11-03）.
^ 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. （原始內容存檔於2014-11-03）.
^ 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 . PMID 19570945. doi:10.1124/mol.109.058057. （原始內容存檔於2017-07-12）.
^ 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. （原始內容存檔於2015-09-19）.

[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. （原始內容存檔於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. （原始內容存檔於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. （原始內容存檔於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. （原始內容存檔於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. （原始內容存檔於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. （原始內容存檔於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 . PMID 19570945. doi:10.1124/mol.109.058057. （原始內容存檔於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. （原始內容存檔於2015-09-19）.

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