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在一项抗体导向酶前体药物疗法(ADEPT)临床研究中对前体药物、活性药物及代谢产物的鉴定。

Identification of prodrug, active drug, and metabolites in an ADEPT clinical study.

作者信息

Springer C J, Poon G K, Sharma S K, Bagshawe K D

机构信息

Department of Medical Oncology, Charing Cross Hospital, London, England.

出版信息

Cell Biophys. 1993 Jan-Jun;22(1-3):9-26. doi: 10.1007/BF03033864.

DOI:10.1007/BF03033864
PMID:7889545
Abstract

Antibody-directed enzyme prodrug therapy (ADEPT) involves two phases. The first is an antibody-enzyme conjugate that localizes to tumor. The second phase is a prodrug that is administered when the enzyme-conjugate has cleared from blood and other nontumor tissues. In the pilot-scale clinical trial, the prodrug has been measured--in the plasma of patients, by liquid chromatography (HPLC) and by liquid chromatography-mass spectrometry (LC-MS). Active drug has been detected and metabolites identified. An indirect measurement of enzyme-conjugate in the plasma of patients has also been developed.

摘要

抗体导向酶前药疗法(ADEPT)包括两个阶段。第一阶段是一种抗体 - 酶偶联物,它会定位于肿瘤部位。第二阶段是在前药,当酶偶联物已从血液和其他非肿瘤组织中清除后给予。在中试规模的临床试验中,通过液相色谱法(HPLC)和液相色谱 - 质谱法(LC - MS)在患者血浆中对前药进行了测定。已检测到活性药物并鉴定出代谢产物。还开发了一种对患者血浆中酶偶联物的间接测量方法。

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本文引用的文献

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Definition of antigenic heterogeneity and modulation among human mammary carcinoma cell populations using monoclonal antibodies to tumor-associated antigens.利用针对肿瘤相关抗原的单克隆抗体对人乳腺癌细胞群体中的抗原异质性和调节进行定义。
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一项针对晚期结直肠癌或其他产生癌胚抗原(CEA)肿瘤患者的抗体导向酶前药疗法(ADEPT)的I期试验。
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Analysis of antibody-enzyme conjugate clearance by investigation of prodrug and active drug in an ADEPT clinical study.在一项抗体导向酶解前药疗法(ADEPT)临床研究中,通过对前体药物和活性药物的研究分析抗体-酶偶联物的清除情况。
Cell Biophys. 1994;24-25:193-207. doi: 10.1007/BF02789230.
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Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate.抗体-碱性磷酸酶偶联物与磷酸依托泊苷联合应用的抗肿瘤作用
Proc Natl Acad Sci U S A. 1988 Jul;85(13):4842-6. doi: 10.1073/pnas.85.13.4842.
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A cytotoxic agent can be generated selectively at cancer sites.一种细胞毒性剂可以在癌症部位被选择性地产生。
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6
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Biochemistry. 1989 Mar 7;28(5):2288-97. doi: 10.1021/bi00431a047.
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Disposition of the prodrug 4-(bis (2-chloroethyl) amino) benzoyl-L-glutamic acid and its active parent drug in mice.前药4-(双(2-氯乙基)氨基)苯甲酰-L-谷氨酸及其活性母体药物在小鼠体内的处置情况。
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Ablation of human choriocarcinoma xenografts in nude mice by antibody-directed enzyme prodrug therapy (ADEPT) with three novel compounds.采用三种新型化合物通过抗体导向酶前药疗法(ADEPT)对裸鼠体内的人绒毛膜癌异种移植瘤进行消融。
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