Metabolism investigation of the peptide-drug conjugate LN005 in rats using UHPLC-HRMS
文献类型：期刊论文
| 作者 | Wang, Weiqiang7; Chen, Chong5,6; Luo, Jing3,4; Tang, Chongzhuang2; Zheng, Yuandong5; Yan, Shu; Yuan, Yali5,6; Zhu, Mingshe2; Diao, Xingxing5,6; Hang, Taijun7 |
| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
 |
| 出版日期 | 2024-01-20 |
| 卷号 | 238页码:11 |
| 关键词 | LN005 Metabolism Peptide -drug conjugates UHPLC-HRMS Doxorubicin |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2023.115860 |
| 通讯作者 | Diao, Xingxing(xxdiao@simm.ac.cn) ; Hang, Taijun(TJ_Hang_CPU@126.com) ; Wang, Hao(wangh@sphchina.com) |
| 英文摘要 | LN005, as a peptide-drug conjugate (PDC), is a conjugate of the homing peptide VAP and doxorubicin (DOX). The exceptional targeting ability of the homing peptide VAP is directed toward glucose-regulated protein (GRP78), a highly expressed protein primarily found in the endoplasmic reticulum of various solid tumors. However, there are limited reports regarding the metabolism of peptide-drug conjugates (PDCs), and the in vivo metabolism of LN005 has yet to be investigated. After intravenous injection of 18 mg/kg LN005 in SD rats, biological samples including plasma, urine, fecal, and bile samples, were collected and analyzed by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). A total of 11 possible metabolites of LN005 were identified. Unchanged LN005 was found to be the main component in rat blood and urine, accounting for 46.46% and 63.79% of the total peak areas, respectively. M1057 was the most abundant metabolite in feces, accounting for 57.65% of the total peak area. Only one metabolite, M398, was identified in rat bile. The metabolism of LN005 is closely related to DOX, and the primary metabolic pathways involved oxidative deamination or hydrolysis, reductive glycosidic cleavage, hydrolytic glycosidic cleavage, and dehydrogenation. |
| WOS关键词 | DOXORUBICIN ; ADRIAMYCIN ; PLASMA |
| 资助项目 | Shanghai Whittlong Pharmaceutical Institute Co., Ltd. ; National Key Research and Development Program of China[2022YFF1202600] ; National Natural Science Foundation of China[82104275] ; National Natural Science Foundation of China[82104276] ; Key Technologies R&D Program of Guangdong Province[2023B1111030004] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001115502600001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308098]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Diao, Xingxing; Hang, Taijun; Wang, Hao |
| 作者单位 | 1.China State Inst Pharmaceut Ind, Natl Pharmaceut Engn Res Ctr, Shanghai, Peoples R China 2.Xenofinder Co Ltd, Suzhou, Peoples R China 3.Shanghai Whittlong Pharmaceut Inst Co Ltd, Shanghai, Peoples R China 4.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 7.China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Weiqiang,Chen, Chong,Luo, Jing,et al. Metabolism investigation of the peptide-drug conjugate LN005 in rats using UHPLC-HRMS[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2024,238:11. |
| APA | Wang, Weiqiang.,Chen, Chong.,Luo, Jing.,Tang, Chongzhuang.,Zheng, Yuandong.,...&Wang, Hao.(2024).Metabolism investigation of the peptide-drug conjugate LN005 in rats using UHPLC-HRMS.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,238,11. |
| MLA | Wang, Weiqiang,et al."Metabolism investigation of the peptide-drug conjugate LN005 in rats using UHPLC-HRMS".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 238(2024):11. |
入库方式： OAI收割
来源：上海药物研究所
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