环特生物荣获第四届东方药理论坛青年优秀论文报告奖

发布时间:2021-12-24

12月16-18日,由中国药理学会和上海市药理学会联合举办的第四届东方药理论坛暨上海市药理学会第二十二届学术年会在上海举行,本届年会采取线上线下相结合的方式。

 

环特生物研究员戴明珠受邀在青年优秀论文报告专场做题为《Validation, optimization and application ofzebrafish developmental toxicity assay forpharmaceuticals under ICH S5(R3) guideline》的学术报告,该研究成果由环特生物、浙江省医学科学院(杭州医学院)安全性评价研究中心、浙江省医学科学院(杭州医学院)浙江省药品安全评价与研究重点实验室、浙江工业大学长三角绿色制药协同创新中心共同发表,荣获第四届东方药理论坛青年优秀论文报告奖(三等奖)。

该研究成果《依照ICH S5(R3)原则建立了斑马鱼发育毒性测试模型及其应用》,具有较高的科研水平和学术价值, 现已发表在SCI期刊《Frontiers in Cell and Developmental Biology》(JCR分区:发育生物学类1区,IF=6.684)上

其是在ICH指导原则下,验证并优化了先前由美国和欧洲的多个实验室间研究报告的斑马鱼发育毒性测定,并证实了:斑马鱼作为一种发育毒性与致畸性试验的替代动物模型,可达到90.3%灵敏度(28/31个阳性化合物对具有致畸作用)和 88.9% (40/45) 总体可预测性。这项研究结果充分支持使用斑马鱼作为替代体内方法来筛选和评估候选药物的发育毒性与致畸性以供监管、使用,可用于新药IND人体临床实验申请。

此次获奖是对环特生物科研实力的再次肯定,截至目前,环特生物已发表斑马鱼科研论文120余篇,申请57项国家发明专利,其中,已获授权27项,主持起草斑马鱼技术应用团体标准11项,其中4项已发布实施。

未来,环特生物将坚持技术创新,以高质量的斑马鱼技术服务,持续推出高水平学术成果,助力更多的科研院所、企业在斑马鱼技术领域实现产学研深度融合,助力健康与美丽产业高质量发展!

 

论文摘要

The zebrafish as an alternative animal model for developmental toxicity testing has been extensively investigated, but its assay protocol was not harmonized yet.

This study has validated and optimized the zebrafish developmental toxicity assay previously reported by multiple inter-laboratory studies in the United States and Europe.

In this study, using this classical protocol, of 31 ICH positive compounds, 23 compounds (74.2%) were teratogenic in zebrafish, 5 had false negative results, and 3 were neither teratogenic nor non-teratogenic according to the protocol standard; of 14 ICH negative compounds, 12 compounds (85.7%) were non-teratogenic in zebrafish and 2 had false positive results.

After we added an additional TI value in the zebrafish treated with testing compounds at 2 dpf along with the original 5 dpf, proposed a new category as the uncategorized compounds for those TI values smaller than the cut-off both at 2 dpf and 5 dpf but inducing toxic phenotypes, and refined the testing concentration ranges, optimized the TI cut-off value from ≥ 10 to ≥ 3 for compounds with refined testing concentrations, this optimized zebrafish developmental assay reached a 90.3% sensitivity (28/31 positive compounds were teratogenic in zebrafish) and 88.9% (40/45) overall predictability.

Our results from this study strongly support the use of zebrafish as an alternative in vivo method for screening and assessing teratogenicity of candidate drugs for regulatory acceptance.