التفاصيل البيبلوغرافية
| العنوان: |
NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies |
| المؤلفون: |
Enrico Pesenti, Laura Gianellini, Jürgen Moll, Michele Caruso, Francesco Fiorentini, Anna De Ponti, Francesco Sola, Jacqueline Lansen, Dario Ballinari, Simona Rizzi, Antonella Ciavolella, Rachele Alzani, Antonella Isacchi, Arturo Galvani, Maria Laura Giorgini, Barbara Valsasina, Italo Beria, Cristina Alli, Nilla Avanzi, Paolo Cappella, Maurizio Rocchetti, Eduard R. Felder, Alessia Casolaro, Ulisse Cucchi |
| المصدر: |
Molecular cancer therapeutics. 11(4) |
| سنة النشر: |
2012 |
| مصطلحات موضوعية: |
Cancer Research, Administration, Oral, Mice, Nude, Antineoplastic Agents, Cell Cycle Proteins, HL-60 Cells, Polo-like kinase, Mice, SCID, Biology, Pharmacology, Protein Serine-Threonine Kinases, PLK1, Mice, Dogs, Cell Line, Tumor, Proto-Oncogene Proteins, Animals, Humans, Kinase activity, Protein kinase A, Chromosome separation, Mitosis, Protein Kinase Inhibitors, Cell Proliferation, Ovarian Neoplasms, Leukemia, Cell growth, Kinase, Haplorhini, Xenograft Model Antitumor Assays, Rats, Oncology, Quinazolines, Pyrazoles, Female, Colorectal Neoplasms |
| الوصف: |
Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase considered to be the master player of cell-cycle regulation during mitosis. It is indeed involved in centrosome maturation, bipolar spindle formation, chromosome separation, and cytokinesis. PLK1 is overexpressed in a variety of human tumors and its overexpression often correlates with poor prognosis. Although five different PLKs are described in humans, depletion or inhibition of kinase activity of PLK1 is sufficient to induce cell-cycle arrest and apoptosis in cancer cell lines and in xenograft tumor models. NMS-P937 is a novel, orally available PLK1-specific inhibitor. The compound shows high potency in proliferation assays having low nanomolar activity on a large number of cell lines, both from solid and hematologic tumors. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits xenograft tumor growth with clear PLK1-related mechanism of action at well-tolerated doses in mice after oral administration. In addition, NMS-P937 shows potential for combination in clinical settings with approved cytotoxic drugs, causing tumor regression in HT29 human colon adenocarcinoma xenografts upon combination with irinotecan and prolonged survival of animals in a disseminated model of acute myelogenous leukemia in combination with cytarabine. NMS-P937, with its favorable pharmacologic parameters, good oral bioavailability in rodent and nonrodent species, and proven antitumor activity in different preclinical models using a variety of dosing regimens, potentially provides a high degree of flexibility in dosing schedules and warrants investigation in clinical settings. Mol Cancer Ther; 11(4); 1006–16. ©2012 AACR. |
| تدمد: |
1538-8514 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee810aaea940cb1b52aca3a096dfdc28
https://pubmed.ncbi.nlm.nih.gov/22319201 |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....ee810aaea940cb1b52aca3a096dfdc28 |
| قاعدة البيانات: |
OpenAIRE |
