O Brien Zhihong, Moghaddam Mehran F
Nitto Biopharma, Inc., 10628 Science Center Dr., San Diego, CA 92121. United States.
OROX BioSciences, Inc., 4971 Sterling Grove Lane, San Diego, CA 92130. United States.
Curr Med Chem. 2017;24(29):3159-3184. doi: 10.2174/0929867324666170523124441.
During lead identification and optimization, the advancement criteria may be driven based on scientific principles, prior experiences, and/or by examining the path paved by approved drugs. However, accessing the discovery data on physicochemical and ADME properties of the approved kinase inhibitors is a monumental task as these are either scattered in the literature or have not been published.
Our goals were: 1) To compile the relevant data on all kinase inhibitors approved prior to 2016 for easy access by the biopharmaceutical community, 2) To provide a retrospective analysis to highlight trends and attributes which may have contributed to the "developability" of these drugs, and 3) To ignite focused debates on what constitutes "actionable", "nice-to-have", and unnecessary data. Such debates bring about more clarity on stage appropriateness of different types of information and prevent confusion due to abundance of unnecessary data, leading to more efficient and less costly drug discovery programs.
A careful and thorough analysis of different bodies of data such as published manuscripts, and available regulatory documents were employed.
We were able to assemble a large body of data on the first thirty kinase inhibitors approved by US FDA since 2001.
In conclusion, we have compiled physicochemical and ADME data on the first 30 approved kinase inhibitors and provided our retrospective analysis, which we hope is helpful in constructing advancement criteria in discovery programs. The examination of this data provides an opportunity to develop an opinion on data prioritization and stage appropriateness of assays.
在先导化合物识别与优化过程中，推进标准可能基于科学原理、以往经验和/或参考已获批药物所走过的道路来制定。然而，获取已获批激酶抑制剂的物理化学性质和药物代谢及药物动力学（ADME）性质的发现数据是一项艰巨的任务，因为这些数据要么分散在文献中，要么尚未发表。
我们的目标是：1）汇编2016年之前获批的所有激酶抑制剂的相关数据，以便生物制药界能够轻松获取；2）进行回顾性分析，以突出可能有助于这些药物“可开发性”的趋势和特性；3）引发关于什么构成“可操作的”、“有帮助的”和不必要数据的集中讨论。此类讨论将使不同类型信息在各阶段的适用性更加清晰，并防止因大量不必要数据导致的混淆，从而使药物发现项目更高效且成本更低。
对已发表的手稿和可用的监管文件等不同数据集进行了仔细而全面的分析。
我们能够收集到自2001年以来美国食品药品监督管理局（US FDA）批准的前三十种激酶抑制剂的大量数据。
总之，我们汇编了前30种获批激酶抑制剂的物理化学性质和ADME数据，并提供了回顾性分析，希望这有助于构建发现项目中的推进标准。对这些数据的研究为就数据优先级和检测方法在各阶段的适用性形成观点提供了机会。
