کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1259002 1496481 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Covalent targeting of acquired cysteines in cancer
ترجمه فارسی عنوان
هدف قرار دادن کووالانسی cysteines اکتسابی در سرطان
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی (عمومی)
چکیده انگلیسی


• Missense mutations in cancer frequently lead to the gain of a cysteine.
• The chemistry of the cysteine thiol allows for covalent modification.
• Covalent drugs have a prolonged or permanent interaction with their targets.
• Covalent targeting of acquired cysteines could be a new personalized cancer therapy.

The thiolate side chain of cysteine has a unique functionality that drug hunters and chemical biologists have begun to exploit. For example, targeting cysteine residues in the ATP-binding pockets of kinases with thiol-reactive molecules has afforded increased selectivity and potency to drugs like imbrutinib, which inhibits the oncogene BTK, and CO-1686 and AZD9291 that target oncogenic mutant EGFR. Recently, disulfide libraries and targeted GDP-mimetics have been used to selectively label the G12C oncogenic mutation in KRAS. We reasoned that other oncogenes contain mutations to cysteine, and thus screened the Catalog of Somatic Mutations in Cancer for frequently acquired cysteines. Here, we describe the most common mutations and discuss how these mutations could be potential targets for cysteine-directed personalized therapeutics.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Current Opinion in Chemical Biology - Volume 30, February 2016, Pages 61–67
نویسندگان
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