کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10593532 | 981811 | 2013 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structure-based design of flavone-based inhibitors of wild-type and T315I mutant of ABL
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The existence of drug resistance caused by mutations in the break-point cluster region-Abelson (BCR-ABL) tyrosine kinase domain remains a clinical challenge due to limited treatment options for effective CML therapies. Here, we report a series of flavone-based common inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of BCR-ABL. The original hit 1 was extensively modified through a structure-based drug design strategy, especially by varying the C7 acetamide appendage of the scaffold to exploit extended interactions with P-loop residues. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of ABL are discussed in detail.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 15, 1 August 2013, Pages 4324-4327
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 15, 1 August 2013, Pages 4324-4327
نویسندگان
Hyeonjeong Choe, Jieun Kim, Sungwoo Hong,