Academic Journal
DPAGT1 Inhibitors of Capuramycin Analogues and Their Antimigratory Activities of Solid Tumors
| العنوان: | DPAGT1 Inhibitors of Capuramycin Analogues and Their Antimigratory Activities of Solid Tumors |
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| المؤلفون: | Mitachi, Katsuhiko, Kansal, Rita G., Hevener, Kirk E., Gillman, Cody D., Hussain, Syed M., Yun, Hyun Gi, Miranda-Carboni, Gustavo A., Glazer, Evan S., Clemons, William M., Jr., Kurosu, Michio |
| المصدر: | Journal of Medicinal Chemistry, 63(19), 10855-10878, (2020-10-08) |
| بيانات النشر: | American Chemical Society |
| سنة النشر: | 2020 |
| المجموعة: | Caltech Authors (California Institute of Technology) |
| مصطلحات موضوعية: | Capuramycin analogues, DPAGT1 inhibitor, Antimigratory activity, Snail zinc-finger transcription factors, E-Cadherin, Synergistic effect, Computational chemistry |
| الوصف: | Capuramycin displays a narrow spectrum of antibacterial activity by targeting bacterial translocase I (MraY). In our program of development of new N-acetylglucosaminephosphotransferase1 (DPAGT1) inhibitors, we have identified that a capuramycin phenoxypiperidinylbenzylamide analogue (CPPB) inhibits DPAGT1 enzyme with an ICâ‚…â‚€ value of 200 nM. Despite a strong DPAGT1 inhibitory activity, CPPB does not show cytotoxicity against normal cells and a series of cancer cell lines. However, CPPB inhibits migrations of several solid cancers including pancreatic cancers that require high DPAGT1 expression in order for tumor progression. DPAGT1 inhibition by CPPB leads to a reduced expression level of Snail but does not reduce E-cadherin expression level at the ICâ‚…â‚€ (DPAGT1) concentration. CPPB displays a strong synergistic effect with paclitaxel against growth-inhibitory action of a patient-derived pancreatic adenocarcinoma, PD002: paclitaxel (ICâ‚…â‚€: 1.25 μM) inhibits growth of PD002 at 0.0024–0.16 μM in combination with 0.10–2.0 μM CPPB (ICâ‚…â‚€: 35 μM). ; © 2020 American Chemical Society. Received: April 16, 2020; Published: September 4, 2020. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM114611. M.K. thanks UTRF (University of Tennessee Health Science Center) for generous financial support (Innovation award R079700292). NMR data were obtained on instruments supported by the NIH Shared Instrumentation Grant. M.K. would like to thank Dr. Michael McNeil (Colorado State University) for providing E. coli B21 WecA strain. The authors gratefully acknowledge Miss Shakiba Eslamimehr and Mr. David Mingle for their efforts in culturing several cancer call lines used in this article. The authors declare no competing financial interest. Dedication: This article is dedicated to the memory of Dr. Isao Kitagawa, Professor Emeritus of Pharmaceutical sciences at Osaka University, an inspirational ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://doi.org/10.1021/acs.jmedchem.0c00545; https://www.ncbi.nlm.nih.gov/pmc/PMC7554145; eprintid:105314 |
| DOI: | 10.1021/acs.jmedchem.0c00545 |
| الاتاحة: | https://www.ncbi.nlm.nih.gov/pmc/PMC7554145 https://doi.org/10.1021/acs.jmedchem.0c00545 |
| Rights: | info:eu-repo/semantics/openAccess ; No commercial reproduction, distribution, display or performance rights in this work are provided. |
| رقم الانضمام: | edsbas.7D76BDE9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.0c00545 |
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