Greber Katarzyna E, Dawgul Małgorzata
Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Al. Gen J. Hallera 107, Gdansk 80-416, Poland.
Curr Top Med Chem. 2017;17(5):620-628. doi: 10.2174/1568026616666160713143331.
Today microbial drug resistance has become a serious problem not only within inpatient setting but also within outpatient setting. Repeated intake and unnecessary usage of antibiotics as well as the transfer of resistance genes are the most important factors that make the microorganisms resistant to conventional antibiotics. A large number of antimicrobials successfully used for prophylaxis and therapeutic purposes have now become ineffective [1, 2]. Therefore, new molecules are being studied to be used in the treatment of various diseases. Some of these molecules are structural compounds based on a combination of peptides, for example, naturally occurring endogenous peptide antibiotics and their synthetic analogues or molecules designed de novo using QSAR (quantitative structureproperty relationships)-based methods [3]. Trying to exploit numerous advantages of antimicrobial peptides such as high potency and selectivity, broad range of targets, potentially low toxicity and low accumulation in tissues, pharmaceutical industry aims to develop them as commercially available drugs and appropriate clinical trials are being conducted [4]. In this paper we define clinical trials steps and describe current status of several antimicrobial peptides under clinical development as well as briefly depict peptide drug formulation.
如今,微生物耐药性不仅在住院环境中,而且在门诊环境中都已成为一个严重问题。抗生素的重复摄入和不必要使用以及耐药基因的转移是使微生物对传统抗生素产生耐药性的最重要因素。大量曾成功用于预防和治疗目的的抗菌药物如今已失效[1,2]。因此,人们正在研究用于治疗各种疾病的新分子。其中一些分子是基于肽组合的结构化合物,例如天然存在的内源性肽抗生素及其合成类似物,或使用基于定量构效关系(QSAR)的方法从头设计的分子[3]。制药行业试图利用抗菌肽的众多优势,如高效性和选择性、广泛的靶点、潜在的低毒性以及在组织中的低蓄积性,致力于将其开发成可上市的药物,并且正在进行适当的临床试验[4]。在本文中,我们定义了临床试验步骤,描述了几种处于临床开发阶段的抗菌肽的现状,并简要阐述了肽类药物制剂。