Wei Jing, Deng Yaping, Zhu Xiaoyun, Xiao Xin, Yang Yang, Tang Chunlei, Chen Jian
Jiaxing Andicon Biotech Co., Ltd., Jiaxing, 314006, China.
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Front Med. 2025 Apr;19(2):347-358. doi: 10.1007/s11684-024-1115-1. Epub 2025 Jan 20.
ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
ADC189是一种新型的帽依赖性核酸内切酶抑制剂药物。在我们的研究中，对其体外和体内的抗病毒疗效进行了评估，并与巴洛沙韦酯和奥司他韦进行了比较。一项针对健康志愿者的首次人体I期研究包括单剂量递增（SAD）和食物效应（FE）部分。在临床前研究中，ADC189对包括H1N1、H3N2、乙型流感病毒和高致病性禽流感在内的多种流感病毒显示出强大的抗病毒活性，与巴洛沙韦酯相当。此外，在感染H1N1的小鼠中，ADC189的抗病毒疗效比奥司他韦好得多。在I期研究中，ADC189迅速代谢为ADC189-I07，其暴露量随剂量成比例增加。终末消除半衰期（T）为76.69至98.28小时。值得注意的是，食物对ADC189的浓度、清除率和暴露量没有影响。它耐受性良好，报告的治疗中出现的不良事件（TEAE）很少，没有严重不良事件（SAE）。ADC189在体外和体内均显示出优异的抗病毒疗效。它在健康志愿者中安全、耐受性良好，具有良好的药代动力学特征，支持其在临床实践中单次口服给药的潜力。
