Pharmacokinetics of recombinant bifunctional fusion proteins.
Pharmacokinetics of recombinant bifunctional fusion proteins.
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DOI：
10.1517/17425255.2012.673585
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发表时间：
2012-05
影响因子：
4.3
通讯作者：
Shen WC
中科院分区：
文献类型：
--
作者：
Chen X;Zaro JL;Shen WC
生物技术的发展使各种重组融合蛋白成为一类新的生物治疗药物。融合蛋白的独特之处在于它们能够融合两个或多个蛋白质结构域，为产生新的功能组合提供了巨大的机会。药代动力学（PK）研究是临床前和临床药物开发的关键组成部分，但尚未对融合蛋白进行充分的探索。缺乏通用的PK模型和研究指南已经成为融合蛋白从基础研究向临床转化的瓶颈。本文回顾了融合蛋白的PK研究现状，涵盖了影响PK的过程。根据它们的PK特性，结合临床或正在开发的例子，对融合蛋白进行了分类。本文还讨论了融合蛋白PK的局限性和未来前景。提出了双功能融合蛋白的PK模型，以强调机制研究对融合蛋白PK特性的全面理解的重要性。该模型建议研究受体结合和随后的单个结构域的细胞内配置，这可能对融合蛋白的PK产生巨大影响。
The development of biotechnology has enabled the creation of various recombinant fusion proteins as a new class of biotherapeutics. The uniqueness of fusion proteins lies in their ability to fuse two or more protein domains, providing vast opportunities to generate novel combinations of functions. Pharmacokinetic (PK) studies, which are critical components in preclinical and clinical drug development, have not been fully explored for fusion proteins. The lack of general PK models and study guidelines has become a bottleneck for translation of fusion proteins from basic research to the clinic. This article reviews the current status of PK studies for fusion proteins, covering the processes that affect PK. According to their PK properties, a classification of fusion proteins is suggested along with examples from the clinic or under development. Current limitations and future perspectives for PK of fusion proteins are also discussed. A PK model for bifunctional fusion proteins is presented to highlight the importance of mechanistic studies for a thorough understanding of the PK properties of fusion proteins. The model suggests investigating the receptor binding and subsequent intracellular disposition of individual domains, which can have dramatic impact on the PK of fusion proteins.
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DOI：
10.1093/protein/14.8.529
发表时间：
2001-08-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Arai, R;Ueda, H;Nagamune, T
通讯作者：
Nagamune, T
影响因子：
5.8
作者：
Barrington, P.;Chien, J. Y.;Hardy, T. A.
通讯作者：
Hardy, T. A.
影响因子：
20.3
作者：
Forero, A;Weiden, PL;Meredith, RF
通讯作者：
Meredith, RF
影响因子：
4.8
作者：
BETTER, M;BERNHARD, SL;FISHWILD, DM
通讯作者：
FISHWILD, DM
影响因子：
11.5
作者：
Bang, S;Nagata, S;Pastan, I
通讯作者：
Pastan, I