Please use this identifier to cite or link to this item:
Title: Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia
Authors: Hart, S.
Goh, K.C.
Novotny-Diermayr, V.
Tan, Y.C.
Madan, B.
Amalini, C.
Ong, L.C.
Kheng, B.
Cheong, A.
Zhou, J. 
Chng, W.J.
Wood, J.M.
Keywords: AML
Issue Date: Nov-2011
Citation: Hart, S., Goh, K.C., Novotny-Diermayr, V., Tan, Y.C., Madan, B., Amalini, C., Ong, L.C., Kheng, B., Cheong, A., Zhou, J., Chng, W.J., Wood, J.M. (2011-11). Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia. Blood Cancer Journal 1 (11) : -. ScholarBank@NUS Repository.
Abstract: FMS-like tyrosine kinase 3 (FLT3) is the most commonly mutated gene found in acute myeloid leukemia (AML) patients and its activating mutations have been proven to be a negative prognostic marker for clinical outcome. Pacritinib (SB1518) is a tyrosine kinase inhibitor (TKI) with equipotent activity against FLT3 (IC 50=22 nM) and Janus kinase 2 (JAK2, IC 50=23 nM). Pacritinib inhibits FLT3 phosphorylation and downstream STAT, MAPK and PI3K signaling in FLT3-internal-tandem duplication (ITD), FLT3-wt cells and primary AML blast cells. Oral administration of pacritinib in murine models of FLT3-ITDdriven AML led to significant inhibition of primary tumor growth and lung metastasis. Upregulation of JAK2 in FLT3-TKIresistant AML cells was identified as a potential mechanism of resistance to selective FLT3 inhibition. This resistance could be overcome by the combined FLT3 and JAK2 activities of pacritinib in this cellular model. Our findings provide a rationale for the clinical evaluation of pacritinib in AML including patients resistant to FLT3-TKI therapy. © 2011 Macmillan Publishers Limited All rights reserved.
Source Title: Blood Cancer Journal
ISSN: 20445385
DOI: 10.1038/bcj.2011.43
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Mar 20, 2019


checked on Mar 20, 2019

Page view(s)

checked on Mar 8, 2019

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.