Title: G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia
Authors: Lee, Hee Kyu
Kim, Hong Woo
Lee, In Yong
Lee, Jungmi
Lee, Jaekyoo
Jung, Dong Sik
Lee, Sang Yeop
Park, Sung Ho
Hwang, Haejun
Choi, Jang-Sik
Kim, Jung-Ho
Kim, Se Won
Kim, Jung Keun
Cools, Jan
Koh, Jong Sung
Song, Ho-Juhn # ×
Issue Date: Apr-2014
Publisher: W.B. Saunders
Series Title: Blood vol:123 issue:14 pages:2209-19
Article number: 10.1182/blood-2013-04-493916
Abstract: Aberrant activations of Fms-like tyrosine receptor kinase (FLT) 3 are implicated in the pathogenesis of 20% to 30% of patients with acute myeloid leukemia (AML). G-749 is a novel FLT3 inhibitor that showed potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays. G-749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. Furthermore, it displayed potent antileukemic activity in bone marrow blasts from AML patients regardless of FLT3 mutation status, including those with little or only minor responses to AC220 or PKC412. Oral administration of G-749 yielded complete tumor regression and increased life span in animal models. Thus, G-749 appears to be a promising next-generation drug candidate for the treatment of relapsed and refractory AML patients with various FLT3-ITD/FLT3-TKD mutants and further shows the ability to overcome drug resistance.
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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