IBI351,a synthetic compound,exerts its anti-tumor effects by specifically,covalently,and irreversibly modifying the 12th cysteine residue of KRAS G12C.However,the pharmacokinetic profile of IBI351 in humans has not ye...IBI351,a synthetic compound,exerts its anti-tumor effects by specifically,covalently,and irreversibly modifying the 12th cysteine residue of KRAS G12C.However,the pharmacokinetic profile of IBI351 in humans has not yet been reported.The current study aimed to investigate the pharmacokinetics and safety of IBI351 in healthy Chinese male subjects.A single oral dose of 600 mg combined with 150μCi[^(14)C]IBI351 was administered to six healthy male volunteers.Blood,urine,and fecal samples were collected at multiple time points to quantify the parent drug and its metabolites.IBI351 showed favorable pharmacokinetic characteristics and was well tolerated by all participants.Seventeen major metabolites were identified in plasma,urine,and feces.The main metabolic pathways included oxidation,hydrogenation,sulfonate conjugation,glucuronide conjugation,and cysteine conjugation.Excretion of IBI351 and its metabolites occurred mainly through feces.Collectively,this first-in-human study provides essential data on the metabolism and safety of IBI351 in Chinese subjects and lays the foundation for its further clinical development as a novel anti-tumor drug.展开更多
为探究梯级水库建设对河流水生态系统的影响,开展梯级水库水生态环境监测预警保护修复提供技术和数据支撑。应用浮游植物生物完整性指数(Phytoplanktonic Index of Biotic Integrity,P-IBI),于2024年3—5月对桐梓河9个采样点开展水生态...为探究梯级水库建设对河流水生态系统的影响,开展梯级水库水生态环境监测预警保护修复提供技术和数据支撑。应用浮游植物生物完整性指数(Phytoplanktonic Index of Biotic Integrity,P-IBI),于2024年3—5月对桐梓河9个采样点开展水生态健康评价。对20个候选指标进行分布范围、判别能力及Pearson相关性分析,筛选出7个核心参数,构建春季桐梓河P-IBI评价体系,并采用比值法确定分级评价标准,对春季桐梓河进行水生态健康评价。研究结果显示,春季桐梓河梯级水库中共鉴定发现浮游植物7门类77属,其中绿藻门29属,硅藻门25属,蓝藻门14属,裸藻门4属,以硅藻-绿藻-蓝藻型为主,优势类群隶属硅藻门。春季桐梓河流域水生态系统总体处于亚健康状况;下游流域水生态健康状况优于上游,各样点水生态健康状况呈上升趋势。梯级水库建设已经对河流的水生态健康造成一定影响,坝前与坝下、梯级水库间的浮游植物群落结构存在明显差异,坝前P-IBI得分分值低于坝后;处于一般、亚健康、健康状态的点位分别为1个、5个和3个。P-IBI参数与多个水理化因子显著相关,表明P-IBI对桐梓河水质污染情况具有一定的指示作用。基于本研究的结果,建议管理部门应进一步控制污染源输入,优化废水污水处理系统,以改善桐梓河流域的水生态系统健康状况。.展开更多
2025年4月29日,IBIS Worldwide在英国伦敦宣布,2025年IBIS全球峰会(IBIS Global Summit 2025)的日程已正式发布,这标志着这场事故车维修行业最具影响力的全球会议进入筹备新阶段。2025年6月24日-26日,来自全球事故车维修领域的高层领导...2025年4月29日,IBIS Worldwide在英国伦敦宣布,2025年IBIS全球峰会(IBIS Global Summit 2025)的日程已正式发布,这标志着这场事故车维修行业最具影响力的全球会议进入筹备新阶段。2025年6月24日-26日,来自全球事故车维修领域的高层领导与决策者将齐聚伊斯坦布尔的博斯普鲁斯瑞士酒店,展开为期2天的高端洞察分享、结构化讨论与战略性人脉拓展。展开更多
基金supported by funding from the 13th Five-Year Plan New Drug Creation Program—Isotope Tracer Technology Platform for Clinical Evaluation of Innovative Drugs(Grant No.2017ZX09304032 with project leaders Jun Zhao and Chen Zhou).
文摘IBI351,a synthetic compound,exerts its anti-tumor effects by specifically,covalently,and irreversibly modifying the 12th cysteine residue of KRAS G12C.However,the pharmacokinetic profile of IBI351 in humans has not yet been reported.The current study aimed to investigate the pharmacokinetics and safety of IBI351 in healthy Chinese male subjects.A single oral dose of 600 mg combined with 150μCi[^(14)C]IBI351 was administered to six healthy male volunteers.Blood,urine,and fecal samples were collected at multiple time points to quantify the parent drug and its metabolites.IBI351 showed favorable pharmacokinetic characteristics and was well tolerated by all participants.Seventeen major metabolites were identified in plasma,urine,and feces.The main metabolic pathways included oxidation,hydrogenation,sulfonate conjugation,glucuronide conjugation,and cysteine conjugation.Excretion of IBI351 and its metabolites occurred mainly through feces.Collectively,this first-in-human study provides essential data on the metabolism and safety of IBI351 in Chinese subjects and lays the foundation for its further clinical development as a novel anti-tumor drug.
文摘为探究梯级水库建设对河流水生态系统的影响,开展梯级水库水生态环境监测预警保护修复提供技术和数据支撑。应用浮游植物生物完整性指数(Phytoplanktonic Index of Biotic Integrity,P-IBI),于2024年3—5月对桐梓河9个采样点开展水生态健康评价。对20个候选指标进行分布范围、判别能力及Pearson相关性分析,筛选出7个核心参数,构建春季桐梓河P-IBI评价体系,并采用比值法确定分级评价标准,对春季桐梓河进行水生态健康评价。研究结果显示,春季桐梓河梯级水库中共鉴定发现浮游植物7门类77属,其中绿藻门29属,硅藻门25属,蓝藻门14属,裸藻门4属,以硅藻-绿藻-蓝藻型为主,优势类群隶属硅藻门。春季桐梓河流域水生态系统总体处于亚健康状况;下游流域水生态健康状况优于上游,各样点水生态健康状况呈上升趋势。梯级水库建设已经对河流的水生态健康造成一定影响,坝前与坝下、梯级水库间的浮游植物群落结构存在明显差异,坝前P-IBI得分分值低于坝后;处于一般、亚健康、健康状态的点位分别为1个、5个和3个。P-IBI参数与多个水理化因子显著相关,表明P-IBI对桐梓河水质污染情况具有一定的指示作用。基于本研究的结果,建议管理部门应进一步控制污染源输入,优化废水污水处理系统,以改善桐梓河流域的水生态系统健康状况。.
文摘2025年4月29日,IBIS Worldwide在英国伦敦宣布,2025年IBIS全球峰会(IBIS Global Summit 2025)的日程已正式发布,这标志着这场事故车维修行业最具影响力的全球会议进入筹备新阶段。2025年6月24日-26日,来自全球事故车维修领域的高层领导与决策者将齐聚伊斯坦布尔的博斯普鲁斯瑞士酒店,展开为期2天的高端洞察分享、结构化讨论与战略性人脉拓展。
