Kinetic target-guided synthesis (KTGS) is an original discovery strategy allowing a target to catalyze the irreversible synthesis of its own ligands from a pool of reagents. Although pioneered almost two decades ago, it only recently proved its usefulness in medicinal chemistry, as exemplified by the increasing number of protein targets used, the wider range of target and pocket types, and the diversity of therapeutic areas explored. In recent years, two new leads for in vivo studies were released. Amidations and multicomponent reactions expanded the armamentarium of reactions beyond triazole formation and two new examples of in cellulo KTGS were also disclosed. Herein, we analyze the origins and the chemical space of both KTGS ligands and warhead-bearing reagents. We review the KTGS timeline focusing on recent cases in order to give medicinal chemists the full scope of this strategy which has great potential for hit discovery and hit or lead optimization.

中文翻译：

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动力学目标指导的合成：达到成熟年龄。

动力学目标导向的合成（KTGS）是一种原始发现策略，允许目标从试剂库催化自身配体的不可逆合成。尽管它在将近20年前就开创了，但直到最近才证明其在药物化学中的实用性，例如所使用的蛋白质靶标数量不断增加，靶标和囊袋类型的范围更广以及所探索的治疗领域的多样性就证明了这一点。近年来，发布了两个新的体内研究线索。酰胺化和多组分反应扩大了反应的设备范围，超越了三唑的形成，并且还公开了纤维素KTGS中的两个新实例。在本文中，我们分析了KTGS配体和带有战斗部的试剂的起源和化学空间。