(S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging

Duan, Xiaojiang; Liu, Futao; Kwon, Hongmok; Byun, Youngjoo; Minn, Il; Cai, Xuekang; Zhang, Jingming; Pomper, Martin G.; Yang, Zhi; Xi, Zhen; Yang, Xing

doi:10.1021/acs.jmedchem.9b02031

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(S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging

Duan, Xiaojiang;
Liu, Futao;
Kwon, Hongmok;
Byun, Youngjoo;
Minn, Il;
외 6명

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44

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48

초록

In an effort to seek novel agents targeting prostate-specific membrane antigen (PSMA), 16 ligands (L1-L16) with structural modifications in S1' binding pocket were synthesized and evaluated for PSMA inhibition. (S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic acids proved to be potent PSMA ligands with K-i values ranging from 0.08 nM to 8.98 nM, which are in the range of or are higher in potency compared to previously published urea-based ligands. Computational docking was performed to study the binding mode of the two most potent ligands discovered. FITC-conjugated L14 could selectively stain PSMA(+) LNCaP cells over PSMA(-) PC3 cells. IRDye800CW conjugated L16 can effectively image tumors in a murine xenograft model of prostate cancer.

키워드

GLUTAMATE CARBOXYPEPTIDASE-II; UREA-BASED INHIBITORS; MEMBRANE ANTIGEN; BIOLOGICAL EVALUATION; PRECLINICAL EVALUATION; RADIOLIGAND THERAPY; GCPII INHIBITORS; PET; DESIGN; AGENTS

제목: (S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging

저자: Duan, Xiaojiang; Liu, Futao; Kwon, Hongmok; Byun, Youngjoo; Minn, Il; Cai, Xuekang; Zhang, Jingming; Pomper, Martin G.; Yang, Zhi; Xi, Zhen; Yang, Xing

DOI: 10.1021/acs.jmedchem.9b02031

발행일: 2020-04-09

유형: Article

저널명: Journal of Medicinal Chemistry

권: 63

호: 7

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