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In vitro anti-myeloma activity of the Aurora kinase inhibitor VE-465.

ABSTRACT: This study characterized the preclinical anti-myeloma activity of VE465, a low molecular weight pan-Aurora kinase inhibitor. After 96-h drug exposure, several multiple myeloma (MM) cell lines were more sensitive to VE465 compared to non-malignant cells. The anti-MM activity of VE465 was maintained in the presence of interleukin-6 and, interestingly, enhanced by co-culture with stromal cells. However, primary MM cells were less responsive than cell lines. Combinations with dexamethasone (Dex), doxorubicin (Doxo) and bortezomib showed no antagonism. Our study highlights the potential role of the tumour microenvironment in modulating the activity of this drug class.

SUBMITTER: Negri JM

PROVIDER: S-EPMC3672411 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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In vitro anti-myeloma activity of the Aurora kinase inhibitor VE-465.

Negri Joseph M JM McMillin Douglas W DW Delmore Jake J Mitsiades Nicholas N Hayden Patrick P Klippel Steffen S Hideshima Teru T Chauhan Dharminder D Munshi Nikhil C NC Buser Carolyn A CA Pollard John J Richardson Paul G PG Anderson Kenneth C KC Mitsiades Constantine S CS

British journal of haematology 20090914 5

This study characterized the preclinical anti-myeloma activity of VE465, a low molecular weight pan-Aurora kinase inhibitor. After 96-h drug exposure, several multiple myeloma (MM) cell lines were more sensitive to VE465 compared to non-malignant cells. The anti-MM activity of VE465 was maintained in the presence of interleukin-6 and, interestingly, enhanced by co-culture with stromal cells. However, primary MM cells were less responsive than cell lines. Combinations with dexamethasone (Dex), do ...[more]

PMID: 19751238

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