دورية أكاديمية
Discovery of New Imidazo[2,1- b ]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising In Vitro and In Vivo Anti-melanoma Activity.
| العنوان: | Discovery of New Imidazo[2,1- b ]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising In Vitro and In Vivo Anti-melanoma Activity. |
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| المؤلفون: | Abdel-Maksoud MS; Medicinal & Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, Egypt., El-Gamal MI; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates.; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt., Lee BS; CTC SCIENCE, 38, Hyundaikia-ro, Paltan-myeon, Hwaseong-si, Gyeonggi-do 18576, Republic of Korea., Gamal El-Din MM; Medicinal & Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, Egypt., Jeon HR; CTCBIO Inc., 450-34, Noha-ri, Paltan-myeon, Hwaseong-si, Gyeonggi-do 18576, Republic of Korea., Kwon D; CTC SCIENCE, 38, Hyundaikia-ro, Paltan-myeon, Hwaseong-si, Gyeonggi-do 18576, Republic of Korea., Ammar UM; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0NR, Scotland, United Kingdom., Mersal KI; Center for Biomaterials, Korea Institute of Science & Technology (KIST), Seongbuk-gu, Hwarangro 14-gil 5, Seoul 136-791, Seoul, Republic of Korea.; Department of Biomolecular Science, University of Science & Technology (UST), Daejeon, Yuseong-gu 34113, Republic of Korea., Ali EMH; Center for Biomaterials, Korea Institute of Science & Technology (KIST), Seongbuk-gu, Hwarangro 14-gil 5, Seoul 136-791, Seoul, Republic of Korea.; Department of Biomolecular Science, University of Science & Technology (UST), Daejeon, Yuseong-gu 34113, Republic of Korea., Lee KT; Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea., Yoo KH; Chemical Kinomics Research Center, Korea Institute of Science & Technology (KIST), Seoul 136-791, Republic of Korea., Han DK; Department of Biomedical Science, CHA University, Gyeonggi 13488, Republic of Korea., Lee JK; Center for Neuro-Medicine, Korea Institute of Science & Technology (KIST), Seongbuk-gu, Hwarangro 14-gil 5, Seoul 136-791, Seoul, Republic of Korea., Kim G; College of Pharmacy, Chosun University, Gwangju 61452, Republic of Korea., Choi HS; College of Pharmacy, Chosun University, Gwangju 61452, Republic of Korea., Kwon YJ; Department of Chemical Engineering and Materials Science, University of California, Irvine, California 92697, United States.; Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, United States., Lee KH; Center for Biomaterials, Korea Institute of Science & Technology (KIST), Seongbuk-gu, Hwarangro 14-gil 5, Seoul 136-791, Seoul, Republic of Korea.; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea., Oh CH; Center for Biomaterials, Korea Institute of Science & Technology (KIST), Seongbuk-gu, Hwarangro 14-gil 5, Seoul 136-791, Seoul, Republic of Korea. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2021 May 27; Vol. 64 (10), pp. 6877-6901. Date of Electronic Publication: 2021 May 17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| 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: | Imidazoles/*chemistry , Protein Kinase Inhibitors/*chemistry , Proto-Oncogene Proteins B-raf/*antagonists & inhibitors , Thiazoles/*chemistry, Animals ; Binding Sites ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Evaluation, Preclinical ; Drug Screening Assays, Antitumor ; Drug Stability ; Half-Life ; Humans ; Imidazoles/metabolism ; Melanoma/drug therapy ; Melanoma/pathology ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Molecular Docking Simulation ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/metabolism ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins B-raf/metabolism ; Structure-Activity Relationship ; Sulfonamides/chemistry ; Thiazoles/metabolism ; Transplantation, Heterologous |
| مستخلص: | BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types. In this work, a series of new (imidazo[2,1- b ]thiazol-5-yl)pyrimidine derivatives possessing a terminal sulfonamide moiety were synthesized. Pan-RAF inhibitory effect of the new series was investigated, and structure-activity relationship is discussed. Antiproliferative activity of the target compounds was tested against the NCI-60 cell line panel. The most active compounds were further tested to obtain their IC |
| المشرفين على المادة: | 0 (Imidazoles) 0 (Protein Kinase Inhibitors) 0 (Sulfonamides) 0 (Thiazoles) 0 (imidazo(2,1-b)thiazole) EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) |
| تواريخ الأحداث: | Date Created: 20210517 Date Completed: 20210621 Latest Revision: 20210621 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1021/acs.jmedchem.1c00230 |
| PMID: | 33999621 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
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| DOI: | 10.1021/acs.jmedchem.1c00230 |