Keratinocyte growth factor in focus: A comprehensive review from structural and functional aspects to therapeutic applications of palifermin

IF 7.7 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biological Macromolecules Pub Date : 2021-11-30 DOI:10.1016/j.ijbiomac.2021.09.151

Solmaz Sadeghi , Hourieh Kalhor , Mohammad Panahi , Hoda Abolhasani , Bahareh Rahimi , Reyhaneh Kalhor , Amirmehdi Mehrabi , Mahsa Vahdatinia , Hamzeh Rahimi

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引用次数: 4

Abstract

Palifermin (Kepivance™) is the first therapeutic approved by the Food and Drug Administration for preventing and managing the oral mucositis provoked by myelotoxic and mucotoxic therapies. Palifermin is a recombinant protein generated from human keratinocyte growth factor (KGF) and imitates the function of endogenous KGF. KGF is an epithelial mitogen involved in various biological processes which belongs to the FGF family. KGF possesses a high level of receptor specificity and plays an important role in tissue repair and maintaining of the mucosal barrier integrity. Based on these unique features, palifermin was developed to enhance the growth of damaged epithelial tissues. Administration of palifermin has shown success in the reduction of toxicities of chemotherapy and radiotherapy, and improvement of the patient's quality of life. Notwithstanding all merits, the clinical application of palifermin is limited owing to its instability and production challenges. Hence, a growing number of ongoing researches are designed to deal with these problems and enhance the physicochemical and pharmaceutical properties of palifermin. In the current review, we discuss KGF structure and function, potential therapeutic applications of palifermin, as well as the latest progress in the production of recombinant human KGF and its challenges ahead.

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聚焦角化细胞生长因子:从结构和功能方面到palifermin的治疗应用的综合综述

Palifermin (Kepivance™)是美国食品和药物管理局批准的第一种用于预防和管理由骨髓毒性和粘膜毒性治疗引起的口腔黏膜炎的治疗药物。Palifermin是由人角质细胞生长因子(KGF)产生的重组蛋白，模仿内源性KGF的功能。KGF是一种参与多种生物过程的上皮有丝分裂原，属于FGF家族。KGF具有高水平的受体特异性，在组织修复和维持粘膜屏障完整性中发挥重要作用。基于这些独特的特性，palifermin被开发用于促进受损上皮组织的生长。palifermin在减少化疗和放疗的毒性和改善患者的生活质量方面取得了成功。尽管有这些优点，palifermin的临床应用由于其不稳定性和生产方面的挑战而受到限制。因此，越来越多的正在进行的研究旨在解决这些问题，提高palifermin的物理化学和药物性能。本文综述了KGF的结构和功能，palifermin的潜在治疗应用，以及重组人KGF生产的最新进展及其面临的挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Biological Macromolecules 生物-生化与分子生物学

CiteScore

13.70

自引率

9.80%

发文量

2728

审稿时长

64 days

期刊介绍： The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.