| Identification | Back Directory | [Name]
2-Pyrimidinamine, 5-chloro-N-[3-cyclopropyl-5-[[(3R,5S)-3,5-dimethyl-1-piperazinyl]methyl]phenyl]-4-(6-methyl-1H-indol-3-yl)-, rel- | [CAS]
2294874-49-8 | [Synonyms]
tuspetinib
HM43239,HM-43239
2-Pyrimidinamine, 5-chloro-N-[3-cyclopropyl-5-[[(3R,5S)-3,5-dimethyl-1-piperazinyl]methyl]phenyl]-4-(6-methyl-1H-indol-3-yl)-, rel- | [Molecular Formula]
C29H33ClN6 | [MOL File]
2294874-49-8.mol | [Molecular Weight]
501.07 |
| Chemical Properties | Back Directory | [Boiling point ]
693.1±65.0 °C(Predicted) | [density ]
1.258±0.06 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light | [solubility ]
DMSO : 125 mg/mL (249.47 mM; Need ultrasonic) | [form ]
Solid | [pka]
14.98±0.30(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Tuspetinib (HM43239) is an orally active and selective FLT3 inhibitor with IC50s of 1.1 nM, 1.8 nM and 1.0 nM for FLT3 WT, FLT3 internal tandem duplication (ITD) and FLT3 D835Y kinases, respectively. Tuspetinib inhibits the kinase activity of FLT3 as a reversible type I inhibitor and modulates p-STAT5, p-ERK, SYK, JAK1/2, and TAK1. Tuspetinib inhibits the proliferation and induces the apoptosis of leukemic cells[1][2][3]. | [in vivo]
Tuspetinib shows the excellent dose proportional antitumor activity in mouse models xenografted with both MV4-11 and MOLM-13 cell lines without any significant toxicity[1].
Tuspetinib prolongs survival in FLT3 ITD/TKD double mutated xenograft mouse models[3]. | [IC 50]
FLT3 WT: 1.1 nM (IC50); FLT3 ITD: 1.8 nM (IC50); FLT3 D835Y: 1.0 nM (IC50) | [References]
[1] Miyoung Lee, et.al. Abstract 804: Antitumor activity of the potent and novel FLT3 inhibitor HM43239 in acute myeloid leukemia. Cancer Res July 1 2018 (78) (13 Supplement) 804.
[2] Naval G. Daver, et.al. HM43239, a Novel Potent Small Molecule FLT3 Inhibitor, in Acute Myeloid Leukemia (AML) with FMS-like Tyrosine Kinase 3 (FLT3) Mutations: Phase 1 /2 Study. Blood 2019; 134 (Supplement_1): 1331.
[3] JiSook Kim, et.al. Abstract 1293: HM43239, a novel FLT3 inhibitor in overcoming resistance for acute myeloid leukemia. Cancer Res July 1 2019 (79) (13 Supplement) 1293. |
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