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MZH29 is a novel potent FLT3 tyrosine kinase inhibitor with activity of overcoming drug resistant mutations in AML

ABSTRACT: In this study, we screened a group of newly synthesized tyrosine kinase inhibitors, and discovered MZH29 was a potent FLT3 inhibitor. Remarkably, MZH29 is well tolerated and effective in the clinically known FLT3 mutants in the constructed BaF3 model cells. MZH29 could also lead to complete tumor regression in the mouse xenograft model and increases survival in the bone marrow engraftment model. Further proteomics study indicates that the inhibition effects of MZH29 and AC220 are in a similar manner. All the results present here support that MZH29 could be a promising candidate for both the FLT3 WT and drug resistance mutant AML.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Apis Mellifera (honeybee)

TISSUE(S): Monocyte, Cell Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Wei Ge

LAB HEAD: Wei Ge

PROVIDER: PXD004278 | Pride | 2016-12-12

REPOSITORIES: pride

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	MS160421-XBH-1.raw	Raw
	MS160421-XBH-10.raw	Raw
	MS160421-XBH-11.raw	Raw
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MZH29 is a novel potent inhibitor that overcomes drug resistance FLT3 mutations in acute myeloid leukemia.

Xu B B Zhao Y Y Wang X X Gong P P Ge W W

Leukemia 20161024 4

More than one-third of patients with acute myeloid leukemia (AML) harbor aberrant mutations in Fms-like tyrosine kinase 3 (FLT3). Among them, the internal tandem duplication (ITD) mutation predicts poor prognosis. MZH29 is a novel FLT3 inhibitor synthesized in our laboratory that showed that cellular and kinase assays sustained inhibitory effects on wild-type and mutant FLT3, including the FLT3-ITD, FLT3-D835H/Y/V and FLT3-K663Q mutants. More importantly, MZH29 retained its potent inhibitory eff ...[more]

PMID: 27773927

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