Singh Rima, Kumar Anoop, Lather Viney, Sharma Ruchika, Pandita Deepti
Department of Pharmacology, DelhiPharmaceutical Sciences and Research University New Delhi, India.
Department of Pharmaceutical Chemistry, Amity University Noida, India.
Expert Opin Drug Saf. 2024 Feb;23(2):231-238. doi: 10.1080/14740338.2023.2248877. Epub 2023 Aug 20.
Calcitonin gene-related peptide (CGRP) antagonists are recently approved for the treatment of migraine.
The main aim of the current study was to find out the association of CGRP antagonists with RP using data mining algorithms integrated with network pharmacological approaches.
The individual case safety reports were extracted using OpenVigil2.1-MedDRA-V17 (2004Q1-2022Q3), the United States Adverse Event Reporting System (US FAERS). The data mining algorithms i.e. reporting odds ratio (ROR) with 95% confidence and proportionality reporting ratio (PRR) with associated chi-square value were calculated along with a minimum of three ICSRs to identify the signal. Further, the network was constructed using Cytoscape 3.7.2. Finally, molecular docking was performed using Glide, Schrodinger Inc.
The PRR ≥2 with a linked chi-square value ≥4, add up of co-occurrence ≥3, and a lower limit of 95% confidence interval of ROR exceeding 2 indicates a positive signal of RP. Further, the network pharmacological and molecular docking results have shown the involvement of insulin-like growth factor 1-receptor (IGF1R) pathways.
The RP is recognized as a novel signal with all CGRP antagonists.
降钙素基因相关肽(CGRP)拮抗剂最近被批准用于治疗偏头痛。
本研究的主要目的是使用与网络药理学方法相结合的数据挖掘算法,找出CGRP拮抗剂与视网膜色素变性(RP)之间的关联。
使用OpenVigil2.1-MedDRA-V17(2004年第一季度至2022年第三季度)、美国不良事件报告系统(US FAERS)提取个体病例安全报告。计算数据挖掘算法,即具有95%置信度的报告比值比(ROR)和具有相关卡方值的比例报告比值(PRR),以及至少三份国际病例安全报告(ICSR)以识别信号。此外,使用Cytoscape 3.7.2构建网络。最后,使用Schrodinger公司的Glide进行分子对接。
PRR≥2且相关卡方值≥4、共现总和≥3以及ROR的95%置信区间下限超过2表明存在RP的阳性信号。此外,网络药理学和分子对接结果显示胰岛素样生长因子1受体(IGF1R)通路参与其中。
RP被认为是所有CGRP拮抗剂的一种新信号。