Identification of ligands that selectively activate the M₁ muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders. Herein, we describe the optimization efforts focused on addressing key physicochemical and safety properties, ultimately leading to the clinical candidate MK-7622, a highly selective positive allosteric modulator of the M₁ muscarinic receptor that has entered Phase II studies in patients with Alzheimer’s disease.

中文翻译：

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MK-7622：一流的M ₁正变构调节剂开发候选人

数十年来一直寻求鉴定能选择性激活M ₁毒蕈碱信号通路的配体，以治疗一系列神经系统疾病和认知障碍。本文中，我们描述了优化工作，重点是解决关键的理化和安全性问题，最终导致了临床候选药物MK-7622，M ₁毒蕈碱受体的高度选择性正变构调节剂，已进入阿尔茨海默氏病患者的II期研究。