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Anti-myeloma activity of the novel 2-aminothienopyrimidine Hsp90 inhibitor NVP-BEP800
- Source :
- British Journal of Haematology. 147:319-327
- Publication Year :
- 2009
- Publisher :
- Wiley, 2009.
-
Abstract
- The 90 kD heat shock protein (Hsp90) molecular chaperone sustains multiple components of oncogenic pathways and has recently emerged as a therapeutic target that is now being clinically tested in a number of malignancies. In order to address formulation issues and to deal with possible resistance mechanisms against small molecule Hsp90 inhibitors, a range of compounds based on different molecular scaffolds are now being developed. The present study preclinically tested the effects of the novel 2-aminothienopyrimidine class Hsp90 inhibitor NVP-BEP800, which is suitable for oral formulations, on multiple myeloma cells from established cell lines and on a larger cohort (n = 40) of primary myeloma samples. The drug effectively and specifically killed the majority of primary myeloma cells in coculture with bone marrow stromal cells and reliably entailed molecular consequences of Hsp90 blockade - such as survival pathway breakdown and client protein depletion - in multiple myeloma cells from cell lines as well as from patients. Collectively, the properties of this novel drug support clinical testing in multiple myeloma.
- Subjects :
- medicine.medical_specialty
Stromal cell
Drug Evaluation, Preclinical
Bone Marrow Cells
Biology
Hsp90 inhibitor
Heat shock protein
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Tumor Cells, Cultured
medicine
Humans
HSP90 Heat-Shock Proteins
Multiple myeloma
Hematology
Cell Death
Dose-Response Relationship, Drug
medicine.disease
Coculture Techniques
Neoplasm Proteins
Lymphoma
Pyrimidines
medicine.anatomical_structure
Cell culture
Immunology
Cancer research
Bone marrow
Stromal Cells
Multiple Myeloma
Subjects
Details
- ISSN :
- 13652141 and 00071048
- Volume :
- 147
- Database :
- OpenAIRE
- Journal :
- British Journal of Haematology
- Accession number :
- edsair.doi.dedup.....c4d87bf13f770289575396be1134702a