[CAS NO. 2294874-49-8] Tuspetinib
PRODUCTS SPECIFICATIONS [2294874-49-8]
DESCRIPTION [2294874-49-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 501.07 |
| Molecular Formula | C29H33ClN6 |
| SMILES | ClC1=CN=C(NC2=CC(C3CC3)=CC(CN4C[C@H](N[C@H](C4)C)C)=C2)N=C1C5=CNC6=CC(C)=CC=C56 |
Summary
HM43239 is an orally active and selective FLT3 inhibitor with IC 50 s of 1.1 nM, 1.8 nM and 1.0 nM for FLT3 WT, FLT3 internal tandem duplication (ITD) and FLT3 D835Y kinases, respectively. HM43239 inhibits the kinase activity of FLT3 as a reversible type I inhibitor and modulates p-STAT5, p-ERK, SYK , JAK1/2, and TAK1. HM43239 inhibits the proliferation and induces the apoptosis of leukemic cells [1] [2] [3] .
IC50 & Target
|
FLT3 WT 1.1 nM (IC 50 ) |
FLT3 ITD 1.8 nM (IC 50 ) |
FLT3 D835Y 1.0 nM (IC 50 ) |
In Vitro
HM43239 potently inhibits the growth of acute myeloid leukemia cell lines harboring FLT3 ITD mutation, such as MV4-11 (IC
50
: 1.3 nM), MOLM-13 (IC
50
: 5.1 nM), and MOLM-14 (IC
50
: 2.9 nM). HM43239 also inhibits KG1a cells (CD34+/CD38- cells) proliferation
[1]
.
HM43239 induces the caspase 3/7-dependent apoptosis of leukemic stem cell (LSC) marker-expressing KG1a cells (CD34+/CD38- cells)
[1]
.
HM43239 potently inhibits phosphorylation of SYK, STAT3, and STAT5 in KG1a cells
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
HM43239 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]
.
HM43239 prolongs survival in FLT3 ITD/TKD double mutated xenograft mouse models
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03850574 | Aptose Biosciences Inc. |
Relapsed or Refractory Acute Myeloid Leukemia
|
March 11, 2019 | Phase 1|Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvent & Solubility
DMSO : 125 mg/mL ( 249.47 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9957 mL | 9.9786 mL | 19.9573 mL |
| 5 mM | 0.3991 mL | 1.9957 mL | 3.9915 mL |
| 10 mM | 0.1996 mL | 0.9979 mL | 1.9957 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.15 mM); Clear solution
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.