Theranostics 2021; 11(1):93-106. doi:10.7150/thno.46593 This issue

Research Paper

LT-171-861, a novel FLT3 inhibitor, shows excellent preclinical efficacy for the treatment of FLT3 mutant acute myeloid leukemia

Zhou Yu#, Jiaying Du#, Hui Hui#, Shaoxin Kan, Tongxin Huo, Kai Zhao, Tao Wu, Qinglong Guo, Na Lu

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
#These authors contributed equally to this study.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Yu Z, Du J, Hui H, Kan S, Huo T, Zhao K, Wu T, Guo Q, Lu N. LT-171-861, a novel FLT3 inhibitor, shows excellent preclinical efficacy for the treatment of FLT3 mutant acute myeloid leukemia. Theranostics 2021; 11(1):93-106. doi:10.7150/thno.46593. Available from

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Graphic abstract

Rationale: Acute myeloid leukemia (AML) is a common type of haematological malignancy. Several studies have shown that neoplasia in AML is enhanced by tyrosine kinase pathways. Recently, given that aberrant activation of Fms-like tyrosine receptor kinase 3 (FLT3) acts as a critical survival signal for cancer cells in 20‒30% patients with AML, inhibition of FLT3 may be a potential therapeutic strategy. Therefore, we identified LT-171-861, a novel kinase inhibitor with remarkable inhibitory activity against FLT3, in preclinical models of AML.

Methods: We determined the inhibitory effects of LT-171-861 in vitro using AML cell lines and transformed BaF3 cells. Target engagement assays were used to verify the interaction between LT-171-861 and FLT3. Finally, a subcutaneous model and a bone marrow engrafted model were used to evaluate the antitumor effects of LT‑171‑861 in vivo.

Results: Our data demonstrated that LT-171-861 had high affinity for FLT3 protein. We also showed that LT-171-861 had an inhibitory effect on FLT3 mutants in cellular assays. Moreover, LT-171-861 had a growth-inhibitory effect on human AML cell lines harboring FLT3 internal tandem duplications (FLT3-ITD) such as FLT3-D835Y, FLT3‑ITD-N676D, FLT3-ITD-D835Y, FLT3-ITD-F691L, FLT3-ITD-Y842C and AML blasts from patients with FLT3-ITD. Furthermore, LT-171-861 showed potent antileukemic efficacy against AML cells. We also show the efficacy of LT‑171-861 in a subcutaneous implantation model and a bone marrow engrafted model in vivo, where administration of LT-171-861 led to almost complete tumor regression and increased survival.

Conclusions: Overall, this study not only identifies LT-171-861 as a potent FLT3 inhibitor, but also provides a rationale for the upcoming clinical trial of LT-171-861 in patients with AML and FLT3-ITD mutations.

Keywords: Acute myeloid leukemia, FLT3, inhibitor, ITD, resistance