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超越新化学实体:基于抗体功能多样性推进药物开发。

Beyond new chemical entities: advancing drug development based on functional versatility of antibodies.

作者信息

Caoili Salvador Eugenio C

机构信息

Department of Biochemistry and Molecular Biology; College of Medicine; University of the Philippines Manila; Manila, Philippines.

出版信息

Hum Vaccin Immunother. 2014;10(6):1639-44. doi: 10.4161/hv.28192. Epub 2014 Mar 14.

Abstract

Antibody-type agents (i.e., antibodies and derivatives thereof) may be produced as clinically valuable antidotes, which conceivably could be developed in tandem with prospective new pharmaceutical products so as to render the risks of clinical trials more acceptable from a regulatory standpoint. Yet, this is but a relatively narrow view of the full potential utility associated with antibody-type agents, the significance of which is appreciated upon reconsidering key aspects of early modern biomedical research (notably major contributions thereto by Nobel Laureate Paul Ehrlich) in light of much more recent advances (e.g., application of immunity-oriented approaches to diseases in general, epitope-specific targeting, abzyme-mediated catalysis, antibody-mediated sustained-release buffering of unbound-ligand concentrations, and enhanced thermal and metabolic stability of deuterated chemical species via the kinetic isotope effect), as conditioned by health-related concerns (e.g., current and anticipated epidemiologic transitions vis-a-vis environmental changes) especially with regard to sustainable development (e.g., emphasizing more efficient resource utilization toward increased global resilience based on greater independence from high-maintenance technological infrastructure). The broader view that thus emerges highlights the urgent need to rebalance the health-research agenda, which presently reflect an overemphasis on small-molecule candidate-drug discovery, in order to advance health based on a comprehensive fundamental synthesis of immunity and pharmacology.

摘要

抗体类药物(即抗体及其衍生物)可作为具有临床价值的解毒剂来生产,理论上可以与潜在的新型药物产品同步开发,以便从监管角度使临床试验风险更易于接受。然而,这只是对抗体类药物全部潜在用途的一种相对狭隘的看法,若结合近期的更多进展(例如,将免疫导向方法普遍应用于疾病、表位特异性靶向、抗体酶介导的催化、抗体介导的未结合配体浓度的缓释缓冲以及通过动力学同位素效应提高氘代化学物质的热稳定性和代谢稳定性),重新审视现代早期生物医学研究的关键方面(尤其是诺贝尔奖获得者保罗·埃尔利希的重大贡献),并考虑到与健康相关的问题(例如,当前和预期的流行病学转变与环境变化的关系),特别是在可持续发展方面(例如,强调更有效地利用资源,以基于减少对高维护技术基础设施的依赖来提高全球复原力),就会认识到其重要性。由此产生的更广阔视角凸显了迫切需要重新平衡健康研究议程,目前该议程过度强调小分子候选药物的发现,以便在免疫与药理学全面基础综合的基础上促进健康。

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本文引用的文献

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