کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8477351 | 1550900 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase
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کلمات کلیدی
FBSFMTCponatinibCMLMEN2PTCGDNFMTCTKIDMSO - DMSOTyrosine kinase - تیروزین کینازRET - حقRearranged during transfection - در ترانسفکشن دوباره تنظیم شده استGatekeeper - دروازه بانDimethyl sulfoxide - دیمتیل سولفواکسیدThyroid cancer - سرطان تیروئیدfetal bovine serum - سرم جنین گاوglial-derived neurotrophic factor - فاکتور نوروترفیک مشتق گلیالAcute lymphoblastic leukemia - لوسمی لنفوبلاستیک حادChronic myeloid leukemia - لوسمی میلوئید مزمنTyrosine kinase inhibitor - مهار کننده تیروزین کینازALL - همهmultiple endocrine neoplasia type 2 - چند نوع نئوپلاسم اندوکرین 2Medullary thyroid carcinoma - کارسینوم تیروئید مدولریPapillary thyroid carcinoma - کارسینوم پاپیلاری تیروئید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase](/preview/png/8477351.png)
چکیده انگلیسی
RET kinase is aberrantly activated in thyroid cancers and in rare cases of lung and colon cancer, and has been validated as a molecular target in these tumors. Vandetanib was recently approved for the treatment of medullary thyroid cancer. However, vandetanib is ineffective in vitro against RET mutants carrying bulky aminoacids at position 804, the gatekeeper residue, similarly to drug-resistant BCR-ABL mutants in chronic myeloid leukemia. Ponatinib is a multi-target kinase inhibitor that was recently approved for treatment-refractory Philadelphia-positive leukemia. We show here potent inhibition of oncogenic RET by ponatinib, including the drug-insensitive V804M/L mutants. Ponatinib inhibited the growth of RET+ and BCR-ABL+ cells with similar potency, while not affecting RET-negative cells. Both in biochemical and in cellular assays ponatinib compared favorably with known RET inhibitors, such as vandetanib, cabozantinib, sorafenib, sunitinib and motesanib, used as reference compounds. We suggest that ponatinib should be considered for the treatment of RET+ tumors, in particular those expressing vandetanib-resistant V804M/L mutations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 377, Issues 1â2, 5 September 2013, Pages 1-6
Journal: Molecular and Cellular Endocrinology - Volume 377, Issues 1â2, 5 September 2013, Pages 1-6
نویسندگان
Luca Mologni, Sara Redaelli, Andrea Morandi, Ivan Plaza-Menacho, Carlo Gambacorti-Passerini,