دورية أكاديمية
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Synthesis and evaluation of 2,5-substituted pyrimidines as small-molecule gankyrin binders.

التفاصيل البيبلوغرافية
العنوان: Synthesis and evaluation of 2,5-substituted pyrimidines as small-molecule gankyrin binders.
المؤلفون: Kanabar D; Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA., Kane EI; Gustaf H. Carlson School of Chemistry & Biochemistry, Clark University, Worcester, MA 01610, USA., Chavan T; Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA., Laflamme TM; Gustaf H. Carlson School of Chemistry & Biochemistry, Clark University, Worcester, MA 01610, USA., Suarez E; Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA., Goyal M; Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA., Gupta V; Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA., Spratt DE; Gustaf H. Carlson School of Chemistry & Biochemistry, Clark University, Worcester, MA 01610, USA., Muth A; Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA.
المصدر: Future medicinal chemistry [Future Med Chem] 2024 Feb; Vol. 16 (3), pp. 239-251. Date of Electronic Publication: 2024 Jan 11.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Future Science Country of Publication: England NLM ID: 101511162 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1756-8927 (Electronic) Linking ISSN: 17568919 NLM ISO Abbreviation: Future Med Chem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Future Science, 2009-
مواضيع طبية MeSH: Tumor Suppressor Protein p53*/metabolism , Neoplasms*/metabolism, Humans ; Proteasome Endopeptidase Complex/metabolism ; Cell Line, Tumor
مستخلص: Background: Gankyrin is an ankyrin-repeat protein that promotes cell proliferation, tumor development and cancer progression when overexpressed. Aim: To design and synthesize a novel series of gankyrin-binding small molecules predicated on a 2,5-pyrimidine scaffold. Materials & methods: The synthesized compounds were evaluated for their antiproliferative activity, ability to bind gankyrin and effects on cell cycle progression and the proteasomal degradation pathway. Results: Compounds 188 and 193 demonstrated the most potent antiproliferative activity against MCF7 and A549 cells, respectively. Both compounds also demonstrated the ability to effectively bind gankyrin, disrupt proteasomal degradation and inhibit cell cycle progression. Conclusion: The 2,5-pyrimidine scaffold exhibits a novel and promising strategy for binding gankyrin and inhibiting cancer cell proliferation.
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معلومات مُعتمدة: R15 GM126432 United States GM NIGMS NIH HHS; SC2 GM139672 United States GM NIGMS NIH HHS; R15GM126432, SC2GM139672 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: breast cancer; gankyrin; lung cancer; protein–protein interactions; tumor suppressor proteins
المشرفين على المادة: 0 (Tumor Suppressor Protein p53)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
تواريخ الأحداث: Date Created: 20240111 Date Completed: 20240130 Latest Revision: 20240519
رمز التحديث: 20240520
مُعرف محوري في PubMed: PMC10853842
DOI: 10.4155/fmc-2023-0124
PMID: 38205637
قاعدة البيانات: MEDLINE
الوصف
تدمد:1756-8927
DOI:10.4155/fmc-2023-0124