Gibson Tony S, Johnson Benjamin, Fanjul Andrea, Halkowycz Petro, Dougan Douglas R, Cole Derek, Swann Steven
Medicinal Chemistry Gastrointestinal Drug Discovery Unit, Takeda California Inc., 10410 Science Center Drive, San Diego, CA 92121, United States.
Medicinal Chemistry CNS Drug Discovery Unit, Takeda California Inc., 10410 Science Center Drive, San Diego, CA 92121, United States.
Bioorg Med Chem Lett. 2017 Apr 15;27(8):1709-1713. doi: 10.1016/j.bmcl.2017.02.079. Epub 2017 Mar 2.
Structure-based drug design is an iterative process that is an established means to accelerate lead optimization, and is most powerful when integrated with information from different sources. Herein is described the use of such methods in conjunction with deconstruction and re-optimization of a diverse series of ASK1 chemotypes along with high-throughput screening that lead to the identification of a novel series of efficient ASK1 inhibitors displaying robust MAP3K pathway inhibition.
基于结构的药物设计是一个迭代过程，是加速先导化合物优化的既定方法，当与来自不同来源的信息整合时最为有效。本文描述了将此类方法与多种ASK1化学类型的解构和重新优化以及高通量筛选相结合的应用，这些工作导致鉴定出一系列新型高效的ASK1抑制剂，它们对丝裂原活化蛋白激酶3（MAP3K）途径具有强大的抑制作用。
