2021,35(1):65-71[2] Guliang Yang,Haiyan Zhong,Xinxin Xia,Zhiwen Qi,Chengzhang Wang,Shiming Li.Potential application of proteolysis targeting chimera(PROTAC)modification technology in natural products for their targeted protein degradation[J].食品科学与人类健康(英文...
PROTAC 是双功能分⼦,由靶蛋⽩的配体、E3 连接酶的配体和连接linker组成,其目的不是抑制靶标而是诱导靶蛋白通过蛋⽩酶体系统被降解。 Schematic of the PROteolysis TArgeting Chimera (PROTAC) technology. (Neklesa, 2017) PROTACs 于 2001年⾸次被报道用于作为⼈⼯靶向泛素连接酶复合物 Skp1-Cullin-...
然而,这项技术PROTAC分子不易穿透细胞膜的缺陷。在寻找E3泛素连接酶的小分子配体时,同样需要解决PROTAC分子难以透过细胞膜的难点。设计合成了一种能够诱导雄激素受体降解的SARM-nutlin PROTAC,这个可以透过细胞膜的PROTAC分子由非甾体雄激素受体配体(SARM)、 MDM2配体nutlin 以及连接链聚乙二醇组成。PROTAC technology c...
[3] Han, Xin, Wenyi Wei, and Yi Sun. "PROTAC degraders with ligands recruiting MDM2 E3 ubiquitin ligase: an updated perspective." Acta Materia Medica (2022).[4] Cecchini, Carlotta, et al. "Exploring the ubiquitin-proteasome system (UPS) through PROTAC technology." Chimia 74.4 (2020): ...
PROTAC technology: opportunities and challenges[J]. ACS medicinal chemistry letters, 2020, 11(3): 237-240. Ishida T, Ciulli A. E3 Ligase Ligands for PROTACs: How They Were Found and How to Discover New Ones[J]. SLAS DISCOVERY: Advancing the Science of Drug Discovery, 2020: ...
其中,最大的优势之一是能够靶向难以成药的靶点或突变蛋白。研究显示,目前药物开发的靶点不到20%,有高达80%的蛋白质靶点是传统药物研发手段无法干预的。另外,PROTAC分子不需要与靶蛋白长时间结合,就能降解靶蛋白使其完全消除功能,有望解决小分子抑制剂常出现的耐药性...
利用在Cereblon结合方面的专业知识,BioTheryX构建了这一种新的、强大的靶向蛋白质降解药物发现引擎——PRODEGY平台(Protein Degrader Technology),旨在设计和开发一流的双功能降解剂(TPD),以解决重大未满足的医疗需求。 据《Nature》,目前的TPD领域主要涵盖三种类型的分子:分子胶(Molecular Glues)、异双功能降解剂(hetero...
[27] Zou, Yutian, Danhui Ma, and Yinyin Wang. "The PROTAC technology in drug development." Cell biochemistry and function 37.1 (2019): 21-30.
[2]Guliang Yang,Haiyan Zhong,Xinxin Xia,Zhiwen Qi,Chengzhang Wang,Shiming Li.Potential application of proteolysis targeting chimera(PROTAC)modification technology in natural products for their targeted protein degradation[J].食品科学与人类健康(英文),2022,11...
Advantages and disadvantages of PROTAC technology The advantage of PROTAC is not only effectively inhibiting the target protein, but also quickly degrading and eliminating the target protein. The catalytic amount of drug can be used to degrade intracellular target protein, thus guaranteeing its great ...