TY - JOUR T1 - Isoliquiritigenin, an Orally Available Natural FLT3 Inhibitor from Licorice, Exhibits Selective Anti–Acute Myeloid Leukemia Efficacy In Vitro and In Vivo JF - Molecular Pharmacology JO - Mol Pharmacol SP - 589 LP - 599 DO - 10.1124/mol.119.116129 VL - 96 IS - 5 AU - Zhi-Xing Cao AU - Yi Wen AU - Jun-Lin He AU - Shen-Zhen Huang AU - Fei Gao AU - Chuan-Jie Guo AU - Qing-Qing Liu AU - Shu-Wen Zheng AU - Dao-Yin Gong AU - Yu-Zhi Li AU - Ruo-Qi Zhang AU - Jian-Ping Chen AU - Cheng Peng Y1 - 2019/11/01 UR - http://molpharm.aspetjournals.org/content/96/5/589.abstract N2 - Licorice is a medicinal herb widely used to treat inflammation-related diseases in China. Isoliquiritigenin (ISL) is an important constituent of licorice and possesses multiple bioactivities. In this study, we examined the selective anti-AML (acute myeloid leukemia) property of ISL via targeting FMS-like tyrosine kinase-3 (FLT3), a certified valid target for treating AML. In vitro, ISL potently inhibited FLT3 kinase, with an IC50 value of 115.1 ± 4.2 nM, and selectively inhibited the proliferation of FLT3–internal tandem duplication (FLT3-ITD) or FLT3-ITD/F691L mutant AML cells. Moreover, it showed very weak activity toward other tested cell lines or kinases. Western blot immunoassay revealed that ISL significantly inhibited the activation of FLT3/Erk1/2/signal transducer and activator of transcription 5 (STAT5) signal in AML cells. Meanwhile, a molecular docking study indicated that ISL could stably form aromatic interactions and hydrogen bonds within the kinase domain of FLT3. In vivo, oral administration of ISL significantly inhibited the MV4-11 flank tumor growth and prolonged survival in the bone marrow transplant model via decreasing the expression of Ki67 and inducing apoptosis. Taken together, the present study identified a novel function of ISL as a selective FLT3 inhibitor. ISL could also be a potential natural bioactive compound for treating AML with FLT3-ITD or FLT3-ITD/F691L mutations. Thus, ISL and licorice might possess potential therapeutic effects for treating AML, providing a new strategy for anti-AML. ER -