NEW METHOD FOR QSAR FOR BIOPHARMACEUTICAL PRODUCTS

我们建议开发一种新的方法来测量治疗剂的疏水特性。这些信息对于定量构效关系（QSAR）分析非常重要。虽然QSAR分析广泛用于普通药物，但由于各种技术原因，它几乎不存在于生物制剂中。新的方法应提供有用的信息，生物药物以及小分子化合物的定量构效关系。该技术是基于一种新的分析应用分配在含水聚合物两相系统。方法是独特的（就所获得的信息类型而言）。定量和通用（可用于不同化学性质的化合物的比较）、廉价和易于执行。因此，它为在发现过程的早期筛选期间获得相关结构相关信息提供了可行的选择。II期部分的主要目标是进一步开发和验证各种生物治疗剂的技术，特别强调肽和常见药物。其他目标包括评估技术分析的各种结构修改，推荐的系统和分析条件的发展，检查相关的筛选应用程序的技术问题，开发一个自动化的测量工作站。并将数据纳入现代QSAR技术。拟定商业应用：新的相关信息的有用的定量结构活性关系（QSAR）分析的治疗药物，应有助于改善合理的药物设计过程。一个快速和廉价的评价一个重要的结构相关的描述符，建议应有助于设计的生物制药和普通药物的改善疗效和安全性。

We propose to develop a new methodology for measurement of hydrophobic properties of therapeutic agents. This information is important for Quantitative Structure-Activity Relationships (QSAR) analyses. While the QSAR analysis is widely used for common drugs, it is virtually non-existent for various technical reasons for biological agents. The new methodology should provide information useful for QSAR of bio pharmaceuticals as well as for small compounds. The technique is based on a novel analytical application of partitioning in aqueous polymer two- phase systems. The methodology is unique (regarding the type of information obtained). quantitative and universal (may be used for comparison of compounds of different chemical nature), inexpensive and easy to perform. It thus provides a viable option for obtaining relevant structure-related information during screening early in the discovery process. The principal objective of the Phase II portion is to further develop and validate the technology for a wide variety of biotherapeutical agents, with specific emphasis on peptides, and for common drugs. Additional objectives include evaluation of the technique for analysis of various structural modifications, development of recommended systems and assay conditions, examination of technical issues related to screening applications, development of an automated measurement workstation. and incorporation of the data into modern QSAR techniques. PROPOSED COMMERCIAL APPLICATION: New relevant information useful for Quantitative Structure-Activity Relationships (QSAR) analysis of therapeutic agents should help improve the rational drug design process. A fast and inexpensive evaluation of an important structure-related descriptor as proposed should help the design of biopharmaceuticals and common drugs of improved efficacy and safety.