https://doi.org/10.4081/hmr.v2i5.743

Pha-739358: a pan-aurora kinase inhibitor

Vol. 2 No. 5: New Drugs in Hematology, Bologna, Italy 5-7 October 2008
Published: June 23, 2009
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Authors

R Paquette
support@pagepress.org
N Shah
C Sawyers
G Martinelli
J Nicoll
M Chalukya
PHA-739358 is a small molecule 3-aminopyrazole derivative with low nanomolar activity against all aurora kinases (AKs). It also inhibits other cancer relevant tyrosine kinases such as wild type and mutated ABL, RET, TRK-A and FGFRs.1,2 PHA-739358 shows a dominant aurora kinase B inhibition-related cellular phenotype and induces a p53 status dependent endoreduplication. The compound has antitumor activity in spontaneous, transgenic and xenograft models of solid and hematologic tumors with occasional cures. It is active in a broad range of BCR-ABL positive and negative cell lines, including T315I BCR-ABL mutants. A decreased phosphorylation of histone H3 under PHA- 739358 treatment has been described as a pharmacodynamic biomarker of aurora kinase B inhibition in human skin at safe doses. Similarly the reduced CRKL phosphorylation documents the activity via BCR-ABL inhibition.1,3

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Paquette, R., Shah, N., Sawyers, C., Martinelli, G., Nicoll, J., & Chalukya, M. (2009). Pha-739358: a pan-aurora kinase inhibitor. Hematology Meeting Reports (formerly Haematologica Reports), 2(5). https://doi.org/10.4081/hmr.v2i5.743
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