PT  - JOURNAL ARTICLE
AU  - HYO JEONG KIM
AU  - HWANI RYU
AU  - HYUN-KYUNG CHOI
AU  - JIE-YOUNG SONG
AU  - SANG-GU HWANG
AU  - JIYEON AHN
TI  - Anti-leukemic Activity of AIU2008 in FLT3-ITD-positive Acute Myeloid Leukemia
AID  - 10.21873/anticanres.14824
DP  - 2021 Feb 01
TA  - Anticancer Research
PG  - 731--737
VI  - 41
IP  - 2
4099  - http://ar.iiarjournals.org/content/41/2/731.short
4100  - http://ar.iiarjournals.org/content/41/2/731.full
SO  - Anticancer Res2021 Feb 01; 41
AB  - Background/Aim: FMS-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase involved in signal transduction underlying survival, proliferation, and differentiation of hematopoietic cells. An internal tandem duplication (ITD) in FLT3 in the juxtamembrane domain is a common mutation causing human acute myeloid leukemia (AML) and activates constitutive signaling. Materials and Methods: We evaluated the novel FLT3 inhibitor 5-(4-fluorophenyl)-N-(naphthalen-1-yl)oxazol-2-amine (AIU2008) for the treatment of AML. Results: AIU2008 was designed by modifying FLT3 inhibitor 7c, and showed improved anti-leukemic efficacy in FLT3-ITD–positive AML cells. Specifically, AIU2008 inhibited cell growth and apoptotic death. In addition, AIU2008 down-regulated DNA repair genes involved in homologous recombination and non-homologous end joining. It contributed to the synergistic inhibition of AML cell growth in combination treatment with PARP inhibitors. Conclusion: AIU2008 is a promising FLT3 targeting agent, and may be used in combination with PARP inhibitors for the treatment of AML.