دورية أكاديمية
Design and Discovery of New Collagen V-Derived FGF2-Blocking Natural Peptides Inhibiting Lung Squamous Cell Carcinoma In Vitro and In Vi vo .
| العنوان: | Design and Discovery of New Collagen V-Derived FGF2-Blocking Natural Peptides Inhibiting Lung Squamous Cell Carcinoma In Vitro and In Vi vo . |
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| المؤلفون: | Kuang K; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Chen X; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Wang M; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Han W; Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China., Qiu X; Key Laboratory of Marine Drug, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.; Laboratory forMarine Drugs and Bioproducts, Qingdao National Laboratory for Marine Scienceand Technology, Ocean University of China, Qingdao 266237, China., Jin T; Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China., Xu R; Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China., Yuan B; Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China., Qian M; Key Laboratory of Marine Drug, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.; Laboratory forMarine Drugs and Bioproducts, Qingdao National Laboratory for Marine Scienceand Technology, Ocean University of China, Qingdao 266237, China., Li C; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Xiang R; Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China., Li F; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Zhang S; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Yang Z; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Du J; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Li D; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Zhang C; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Wang Q; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China., Jia T; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2024 Aug 08; Vol. 67 (15), pp. 12660-12675. Date of Electronic Publication: 2024 Jul 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Fibroblast Growth Factor 2*/antagonists & inhibitors , Fibroblast Growth Factor 2*/metabolism , Fibroblast Growth Factor 2*/chemistry , Lung Neoplasms*/drug therapy , Lung Neoplasms*/pathology , Lung Neoplasms*/metabolism , Carcinoma, Squamous Cell*/drug therapy , Carcinoma, Squamous Cell*/pathology , Carcinoma, Squamous Cell*/metabolism , Drug Design* , Peptides*/pharmacology , Peptides*/chemistry , Peptides*/chemical synthesis, Humans ; Animals ; Mice ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/chemical synthesis ; Cell Line, Tumor ; Molecular Dynamics Simulation ; Mice, Nude |
| مستخلص: | Aberrant FGF2/FGFR signaling is implicated in lung squamous cell carcinoma (LSCC), posing treatment challenges due to the lack of targeted therapeutic options. Designing drugs that block FGF2 signaling presents a promising strategy different from traditional kinase inhibitors. We previously reported a ColVα1-derived fragment, HEPV (127AA), that inhibits FGF2-induced angiogenesis. However, its large size may limit therapeutic application. This study combines rational peptide design, molecular dynamics simulations, knowledge-based prediction, and GUV and FRET assays to identify smaller peptides with FGF2-blocking properties. We synthesized two novel peptides, HBS-P1 (45AA) and HBS-P2 (66AA), that retained the heparin-binding site. Both peptides demonstrated anti-LSCC and antiangiogenesis properties in cell viability and microvessel network induction assays. In two LSCC subcutaneous models, HBS-P1, with its affinity for FGF2 and enhanced penetration ability, demonstrated substantial therapeutic potential without apparent toxicities. Our study provides the first evidence supporting the development of collagen V-derived natural peptides as FGF2-blocking agents for LSCC treatment. |
| المشرفين على المادة: | 103107-01-3 (Fibroblast Growth Factor 2) 0 (Peptides) 0 (Antineoplastic Agents) |
| تواريخ الأحداث: | Date Created: 20240724 Date Completed: 20240808 Latest Revision: 20240808 |
| رمز التحديث: | 20240808 |
| DOI: | 10.1021/acs.jmedchem.4c00654 |
| PMID: | 39045829 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
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| DOI: | 10.1021/acs.jmedchem.4c00654 |