کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10596242 | 981897 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacophore identification of c-Myc inhibitor 10074-G5
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
A structure-activity relationship (SAR) study of the c-Myc (Myc) inhibitor 10074-G5 (N-([1,1â²-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine, 1) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore. Whilst the 7-nitrobenzofurazan was found to be critical for inhibitory activity, the ortho-biphenyl could be replaced with a para-carboxyphenyl group to furnish the new inhibitor JY-3-094 (3q). Around five times as potent as the lead with an IC50 of 33 μM for disruption of the Myc-Max heterodimer, JY-3-094 demonstrated excellent selectivity over Max-Max homodimers, with no apparent effect at 100 μM. Importantly, the carboxylic acid of JY-3-094 improves the physicochemical properties of the lead compound, which will facilitate the incorporation of additional hydrophobicity that might enhance Myc inhibitory activity further still.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 1, 1 January 2013, Pages 370-374
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 1, 1 January 2013, Pages 370-374
نویسندگان
Jeremy L. Yap, Huabo Wang, Angela Hu, Jay Chauhan, Kwan-Young Jung, Robert B. Gharavi, Edward V. Prochownik, Steven Fletcher,