Metabolite characterisation of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS
文献类型:期刊论文
作者 | Yuan, Yali2,3; Wang, Weiqiang6; Luo, Jing1,5; Tang, Chongzhuang4; Zheng, Yuandong2; Yu, Jinghua2; Xu, Honghong5; Zhu, Mingshe4; Hang, Taijun6; Wang, Hao7 |
刊名 | XENOBIOTICA |
出版日期 | 2024-01-05 |
页码 | 9 |
ISSN号 | 0049-8254 |
关键词 | peptide-drug conjugate PDC LN005 metabolite identification liver S9s |
DOI | 10.1080/00498254.2023.2289635 |
通讯作者 | Wang, Hao(wangh@sphchina.com) ; Diao, Xingxing(xxdiao@simm.ac.cn) |
英文摘要 | LN005 is a peptide-drug conjugate (PDC) targeting glucose-regulated protein 78 (GRP78) to treat several types of cancer, such as breast, colon, and prostate cancer.As a new drug modality, understanding its metabolism and elimination pathways will help us to have a whole picture of it. Currently, there are no metabolic studies on LN005; therefore, this study aimed to investigate the metabolism of LN005, clarify its metabolic profile in the liver S9s of different species, and identify the major metabolic pathways and differences between species.The incubation samples were measured by ultra-high performance liquid chromatography combined with orbitrap tandem mass spectrometry (UHPLC-Orbitrap-HRMS).The results showed that LN005 was metabolised by liver S9s, and four metabolites were identified. The main metabolic pathway of LN005 in liver S9s was oxidative deamination to ketone or hydrolysis. Similar metabolic profiles were observed in mouse, rat, dog, monkey, and human liver S9s, indicating no differences between these four animal species and humans.This study provides information for the structural modification and optimisation of LN005 and affords a reference for subsequent animal experiments and human metabolism of other PDCs. |
WOS关键词 | DOXORUBICIN ; GRP78 ; PHARMACOKINETICS ; IDENTIFICATION ; DISCOVERY |
资助项目 | the National Key R&D Program of China ; Shanghai Whittlong Pharmaceutical Institute[2022YFF1202600] ; National Key R&D Program of China[2023B1111030004] ; Key Technologies R&D Program of Guangdong Province[82104276] ; Key Technologies R&D Program of Guangdong Province[82104275] ; National Natural Science Foundation of China |
WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
语种 | 英语 |
出版者 | TAYLOR & FRANCIS LTD |
WOS记录号 | WOS:001138462400001 |
源URL | [http://119.78.100.183/handle/2S10ELR8/308550] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Wang, Hao; Diao, Xingxing |
作者单位 | 1.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 4.XenoFinder Co Ltd, Dept Biotransformat, Suzhou, Peoples R China 5.Shanghai Whittlong Pharmaceut Inst Co Ltd, Shanghai, Peoples R China 6.China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing, Peoples R China 7.China State Inst Pharmaceut Ind, Natl Pharmaceut Engn & Res Ctr, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Yuan, Yali,Wang, Weiqiang,Luo, Jing,et al. Metabolite characterisation of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS[J]. XENOBIOTICA,2024:9. |
APA | Yuan, Yali.,Wang, Weiqiang.,Luo, Jing.,Tang, Chongzhuang.,Zheng, Yuandong.,...&Diao, Xingxing.(2024).Metabolite characterisation of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS.XENOBIOTICA,9. |
MLA | Yuan, Yali,et al."Metabolite characterisation of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS".XENOBIOTICA (2024):9. |
入库方式: OAI收割
来源:上海药物研究所
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