Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
J Med Chem. 2021 Jun 24;64(12):8101-8103. doi: 10.1021/acs.jmedchem.1c00843. Epub 2021 May 21.
Chemical modification of the prototype CB1R ago-PAM, GAT211, yielded new CB1R allosteric modulators (-)-(,)- and (+)-(,)-, which showed significant bias for CB1R signaling pathways, as supported by docking studies. Compound efficiently lowered elevated intraocular pressure when it is due to an increase in endocannabinoid tone. This article may open new avenues to meet the therapeutic needs presented by glaucoma.
通过对原型 CB1R 前激动剂 GAT211 进行化学修饰，得到了新型 CB1R 变构调节剂(-)-(,)-和 (+)-(,)-，这些调节剂的构象研究支持其对 CB1R 信号通路具有显著的偏向性。化合物在因内源性大麻素水平升高而导致眼内压升高时，能有效降低眼内压。本文可能为满足青光眼的治疗需求开辟新途径。
