دورية أكاديمية
Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines.
| العنوان: | Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. |
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| المؤلفون: | Payton M; Department of Oncology Research, Amgen Inc., Thousand Oaks, California 91320, USA. mpayton@amgen.com, Bush TL, Chung G, Ziegler B, Eden P, McElroy P, Ross S, Cee VJ, Deak HL, Hodous BL, Nguyen HN, Olivieri PR, Romero K, Schenkel LB, Bak A, Stanton M, Dussault I, Patel VF, Geuns-Meyer S, Radinsky R, Kendall RL |
| المصدر: | Cancer research [Cancer Res] 2010 Dec 01; Vol. 70 (23), pp. 9846-54. Date of Electronic Publication: 2010 Oct 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Drug Resistance, Neoplasm/*drug effects , Neoplasms/*drug therapy , Phthalazines/*pharmacology , Protein Kinase Inhibitors/*pharmacology , Protein Serine-Threonine Kinases/*antagonists & inhibitors, Adult ; Animals ; Aurora Kinase A ; Aurora Kinase B ; Aurora Kinases ; Benzamides/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Clinical Trials as Topic ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Female ; HCT116 Cells ; HeLa Cells ; Histones/metabolism ; Humans ; Mice ; Mice, Nude ; Mutation ; Neoplasms/enzymology ; Neoplasms/pathology ; Organophosphates/pharmacology ; Paclitaxel/pharmacology ; Phosphorylation/drug effects ; Piperazines/pharmacology ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Pyrazoles/pharmacology ; Quinazolines/pharmacology ; Xenograft Model Antitumor Assays |
| مستخلص: | In mammalian cells, the aurora kinases (aurora-A, -B, and -C) play essential roles in regulating cell division. The expression of aurora-A and -B is elevated in a variety of human cancers and is associated with high proliferation rates and poor prognosis, making them attractive targets for anticancer therapy. AMG 900 is an orally bioavailable, potent, and highly selective pan-aurora kinase inhibitor that is active in taxane-resistant tumor cell lines. In tumor cells, AMG 900 inhibited autophosphorylation of aurora-A and -B as well as phosphorylation of histone H3 on Ser(10), a proximal substrate of aurora-B. The predominant cellular response of tumor cells to AMG 900 treatment was aborted cell division without a prolonged mitotic arrest, which ultimately resulted in cell death. AMG 900 inhibited the proliferation of 26 tumor cell lines, including cell lines resistant to the antimitotic drug paclitaxel and to other aurora kinase inhibitors (AZD1152, MK-0457, and PHA-739358), at low nanomolar concentrations. Furthermore, AMG 900 was active in an AZD1152-resistant HCT116 variant cell line that harbors an aurora-B mutation (W221L). Oral administration of AMG 900 blocked the phosphorylation of histone H3 in a dose-dependent manner and significantly inhibited the growth of HCT116 tumor xenografts. Importantly, AMG 900 was broadly active in multiple xenograft models, including 3 multidrug-resistant xenograft models, representing 5 tumor types. AMG 900 has entered clinical evaluation in adult patients with advanced cancers and has the potential to treat tumors refractory to anticancer drugs such as the taxanes. |
| المشرفين على المادة: | 0 (2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate) 0 (Benzamides) 0 (Histones) 0 (N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine) 0 (Organophosphates) 0 (Phthalazines) 0 (Piperazines) 0 (Protein Kinase Inhibitors) 0 (Pyrazoles) 0 (Quinazolines) 234335M86K (tozasertib) EC 2.7.11.1 (AURKB protein, human) EC 2.7.11.1 (Aurka protein, mouse) EC 2.7.11.1 (Aurkb protein, mouse) EC 2.7.11.1 (Aurora Kinase A) EC 2.7.11.1 (Aurora Kinase B) EC 2.7.11.1 (Aurora Kinases) EC 2.7.11.1 (Protein Serine-Threonine Kinases) M3X659D0FY (danusertib) P88XT4IS4D (Paclitaxel) |
| تواريخ الأحداث: | Date Created: 20101012 Date Completed: 20110210 Latest Revision: 20220601 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1158/0008-5472.CAN-10-3001 |
| PMID: | 20935223 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
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| DOI: | 10.1158/0008-5472.CAN-10-3001 |