دورية أكاديمية
XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC.
| العنوان: | XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC. |
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| المؤلفون: | Zhang Y; University of Virginia, Department of Microbiology, PO Box 800168, Charlottesville, Virginia, 22903, USA. ra6u@virginia.edu, Guessous F, Kofman A, Schiff D, Abounader R |
| المصدر: | IDrugs : the investigational drugs journal [IDrugs] 2010 Feb; Vol. 13 (2), pp. 112-21. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Thomson Reuters (Scientific) Ltd Country of Publication: England NLM ID: 100883655 Publication Model: Print Cited Medium: Internet ISSN: 2040-3410 (Electronic) Linking ISSN: 13697056 NLM ISO Abbreviation: IDrugs Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London, U.K. : Thomson Reuters (Scientific) Ltd Original Publication: London : Current Drugs Ltd., |
| مواضيع طبية MeSH: | Antineoplastic Agents/*pharmacology , Protein Kinase Inhibitors/*pharmacology, Animals ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Carcinoma, Medullary/drug therapy ; Carcinoma, Medullary/physiopathology ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/physiopathology ; Clinical Trials as Topic ; Drug Evaluation, Preclinical ; Glioblastoma/drug therapy ; Glioblastoma/physiopathology ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/physiopathology ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use ; Thyroid Neoplasms/drug therapy ; Thyroid Neoplasms/physiopathology |
| مستخلص: | XL-184 (BMS-907351), under development by Exelixis Inc and Bristol-Myers Squibb Co, is a pan-tyrosine kinase inhibitor for the potential oral treatment of medullary thyroid cancer, glioblastoma multiforme and NSCLC. The prinicipal targets of XL-184 are MET, VEGFR-2 and RET, but the drug is also reported to display inhibitory activity against KIT, FLT3 and TEK. Preclinical studies demonstrated that XL-184 potently inhibited multiple receptor tyrosine kinases in various cancer cell lines and animal xenograft models, and that the drug exhibited significant oral bioavailability and blood-brain barrier penetration. A phase I clinical trial in patients with advanced solid malignancies indicated that XL-184 accumulated dose-dependently in the plasma and had a long terminal half-life. A phase II trial in patients with progressive or recurrent glioblastoma revealed modest but promising median progression-free survival. Toxicity and side effects for the drug have generally been of low-to-moderate severity. At the time of publication, three additional trials of XL-184 were recruiting patients, including a phase I trial in combination with standard of care in patients with glioblastoma, a phase I/II trial in combination with erlotinib in patients with NSCLC, and a phase III trial in patients with medullary thyroid cancer. |
| Number of References: | 64 |
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| معلومات مُعتمدة: | R01 CA134843 United States CA NCI NIH HHS; R01 CA134843-03 United States CA NCI NIH HHS; R01 NS045209 United States NS NINDS NIH HHS; R01 NS045209-09 United States NS NINDS NIH HHS |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Protein Kinase Inhibitors) |
| تواريخ الأحداث: | Date Created: 20100204 Date Completed: 20100421 Latest Revision: 20211020 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3268517 |
| PMID: | 20127563 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2040-3410 |
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