LY2119620 is a muscarinic M2/M4 receptor-selective positive allosteric modulator [1]. LY2119620 can alter the intracellular conformational ensemble of the acetylcholine (ACh)-bound M2 receptor (M2R), leading to an increase in the recruitment of β-arrestin and simultaneously inhibiting the activation of G proteins[2]. LY2119620 has been widely used as a model compound for the development of novel radiotracers that can directly label muscarinic allosteric sites[3].
In vivo, LY2119620 (100µM; 10 µl) was injected once every four days for 4 weeks, resulting in a thinning of the retina and choroid thickness in male guinea pigs with form deprivation myopia (FDM), and significant increases in the degree of myopia and the K+ concentration in the retina[4].
References:
[1] Croy C H, Schober D A, Xiao H, et al. Characterization of the novel positive allosteric modulator, LY2119620, at the muscarinic M2 and M4 receptors[J]. Molecular pharmacology, 2014, 86(1): 106-115.
[2] Xu J, Wang Q, Hübner H, et al. Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor[J]. Nature Communications, 2023, 14(1): 376.
[3] Schober D A, Croy C H, Xiao H, et al. Development of a radioligand,[3H] LY2119620, to probe the human M2 and M4 muscarinic receptor allosteric binding sites[J]. Molecular pharmacology, 2014, 86(1): 116-123.
[4] Zhou H, Zhou G, Yang Q, et al. Evidence for M2 Muscarinic Receptor Antagonist Delay of Myopia Development Through Activation of Kir3. 4 Channel in the Retina of Guinea Pigs[J]. Investigative Ophthalmology & Visual Science, 2025, 66(9): 5-5.
LY2119620是一种muscarinic M2/M4受体选择性正性变构调节剂[1]。LY2119620通过改变acetylcholine (ACh)结合的M2受体(M2R)的细胞内构象集合，促进β-arrestin蛋白的募集，同时抑制G蛋白的激活[2]。LY2119620已被广泛用作模型化合物，用于开发能够直接标记毒蕈碱变构位点的新型放射性示踪剂[3]。
在体内，对形觉剥夺性近视（FDM）雄性豚鼠每四天注射一次LY2119620（100µM；10 µl），持续4周，可导致视网膜和脉络膜厚度变薄，并显著加重近视程度，同时提高视网膜中的K+浓度[4]。