蛋白降解靶向嵌合体

蛋白降解靶向嵌合体^[1]（proteolysis targeting chimera，PROTAC）是一种利用小分子化合物来调节蛋白水平的靶向蛋白质降解技术^[2]。PROTAC相对于传统小分子药物具有不同的作用模式，可以利用独特的靶点将蛋白送入蛋白酶体，以实现化学敲降蛋白的目的^[3]^[4]。它的核心概念为利用人工小分子化合物召集一种特定的泛素连接酶，并通过实现靶蛋白的泛素化来降解蛋白^[5]。这一技术由于降解时模式为反复迭代，在靶蛋白突变等情况下相比传统的药物有更好的耐受性^[6]。如今，PROTAC技术是相关制药研究中的热门方向^[6]^[7]^[8]。

参考文献

^ 刘昭祥,刘森.蛋白降解靶向嵌合体临床前及临床研究进展[J].生物工程学报, 2023, 39(9):3615-3627.
^ An, Sainan; Fu, Liwu. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018, 36 [2020-05-26]. ISSN 2352-3964. doi:10.1016/j.ebiom.2018.09.005. （原始内容存档于2021-02-07）（英语）.
^ Neklesa, Taavi K.; Winkler, James D.; Crews, Craig M. Targeted protein degradation by PROTACs. Pharmacology & Therapeutics. 2017, 174 [2020-05-26]. ISSN 0163-7258. doi:10.1016/j.pharmthera.2017.02.027. （原始内容存档于2022-07-07）（英语）.
^ Gadd, Morgan S.; Testa, Andrea; Lucas, Xavier; Chan, Kwok-Ho; Chen, Wenzhang; Lamont, Douglas J.; Zengerle, Michael; Ciulli, Alessio. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nature Chemical Biology. 2017, 13 (5) [2020-05-26]. ISSN 1552-4469. doi:10.1038/nchembio.2329. （原始内容存档于2021-02-08）（英语）.
^ Sakamoto, Kathleen M.; Kim, Kyung B.; Kumagai, Akiko; Mercurio, Frank; Crews, Craig M.; Deshaies, Raymond J. Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation. Proceedings of the National Academy of Sciences. 2001, 98 (15) [2020-05-26]. ISSN 0027-8424. doi:10.1073/pnas.141230798. （原始内容存档于2021-02-08）（英语）.
^ ^6.0 ^6.1 Huang, Xiaodong; Dixit, Vishva M. Drugging the undruggables: exploring the ubiquitin system for drug development. Cell Research. 2016, 26 (4) [2020-05-26]. ISSN 1748-7838. doi:10.1038/cr.2016.31. （原始内容存档于2021-03-09）（英语）.
^ 王瑞峰; 杨博文; 赵冬梅; 程卯生. 蛋白降解靶向嵌合体(PROTAC)的研究进展. 中国药物化学杂志. 2019, 29 (3). doi:10.14142/j.cnki.cn21－1313/r.2019.03.011 （英语）. ^{[永久失效链接]}
^ Zou, Yutian; Ma, Danhui; Wang, Yinyin. The PROTAC technology in drug development. Cell Biochemistry and Function. 2019, 37 (1) [2020-05-26]. ISSN 1099-0844. doi:10.1002/cbf.3369. （原始内容存档于2021-02-07）（英语）.

[1] 刘昭祥,刘森.蛋白降解靶向嵌合体临床前及临床研究进展[J].生物工程学报, 2023, 39(9):3615-3627.

[期刊1-2] An, Sainan; Fu, Liwu. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018, 36 [2020-05-26]. ISSN 2352-3964. doi:10.1016/j.ebiom.2018.09.005. （原始内容存档于2021-02-07）（英语）.

[期刊2-3] Neklesa, Taavi K.; Winkler, James D.; Crews, Craig M. Targeted protein degradation by PROTACs. Pharmacology & Therapeutics. 2017, 174 [2020-05-26]. ISSN 0163-7258. doi:10.1016/j.pharmthera.2017.02.027. （原始内容存档于2022-07-07）（英语）.

[期刊3-4] Gadd, Morgan S.; Testa, Andrea; Lucas, Xavier; Chan, Kwok-Ho; Chen, Wenzhang; Lamont, Douglas J.; Zengerle, Michael; Ciulli, Alessio. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nature Chemical Biology. 2017, 13 (5) [2020-05-26]. ISSN 1552-4469. doi:10.1038/nchembio.2329. （原始内容存档于2021-02-08）（英语）.

[期刊4-5] Sakamoto, Kathleen M.; Kim, Kyung B.; Kumagai, Akiko; Mercurio, Frank; Crews, Craig M.; Deshaies, Raymond J. Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation. Proceedings of the National Academy of Sciences. 2001, 98 (15) [2020-05-26]. ISSN 0027-8424. doi:10.1073/pnas.141230798. （原始内容存档于2021-02-08）（英语）.

[期刊5-6] 6.0 ^6.1 Huang, Xiaodong; Dixit, Vishva M. Drugging the undruggables: exploring the ubiquitin system for drug development. Cell Research. 2016, 26 (4) [2020-05-26]. ISSN 1748-7838. doi:10.1038/cr.2016.31. （原始内容存档于2021-03-09）（英语）.

[期刊6-7] 王瑞峰; 杨博文; 赵冬梅; 程卯生. 蛋白降解靶向嵌合体(PROTAC)的研究进展. 中国药物化学杂志. 2019, 29 (3). doi:10.14142/j.cnki.cn21－1313/r.2019.03.011 （英语）. ^{[永久失效链接]}

[期刊7-8] Zou, Yutian; Ma, Danhui; Wang, Yinyin. The PROTAC technology in drug development. Cell Biochemistry and Function. 2019, 37 (1) [2020-05-26]. ISSN 1099-0844. doi:10.1002/cbf.3369. （原始内容存档于2021-02-07）（英语）.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]