| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
HM43239 targets FLT3 (FMS-like tyrosine kinase 3), a receptor tyrosine kinase commonly mutated in acute myeloid leukemia (AML). It potently inhibits various FLT3 mutations, including wild-type, ITD, TKD, and double mutants. Its ability to inhibit a broad range of mutations, including those associated with resistance, is a key feature.
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|---|---|
| ln Vitro |
In vitro, HM43239 inhibits FLT3 kinase activity with low nanomolar IC50 values: 1.1 nM for FLT3 WT, 1.8 nM for FLT3 ITD, and 1.0 nM for FLT3 D835Y. It inhibits the proliferation and induces the apoptosis of leukemic cells. These results demonstrate its potent activity against FLT3-driven malignancies.
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| ln Vivo |
In vivo, HM43239 prolongs survival in FLT3 ITD/TKD double-mutated xenograft mouse models. Its oral activity and ability to inhibit the most common FLT3 mutations make it a promising therapeutic agent for AML. These studies provide strong evidence for its potential clinical benefit.
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| Enzyme Assay |
In vitro kinase assays are performed using purified FLT3 kinases (WT, ITD, TKD). The compound is incubated with the kinase and a substrate, and the degree of phosphorylation is measured to determine IC50 values. These assays confirm its potency and selectivity.
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| Cell Assay |
Leukemic cell lines harboring FLT3 mutations are treated with HM43239. Cell proliferation and apoptosis are measured. The compound's effect on downstream signaling pathways, such as STAT5 and ERK, is also assessed. These cellular assays are crucial for understanding its mechanism of action.
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| Animal Protocol |
The in vivo efficacy of HM43239 is evaluated in mouse xenograft models. Mice bearing FLT3-mutated tumors are treated orally with the compound. Tumor growth inhibition and survival are measured as key endpoints.
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| ADME/Pharmacokinetics |
HM43239 is orally bioavailable. Its pharmacokinetic properties, including absorption, distribution, metabolism, and excretion, would be characterized in preclinical species to support its development as an oral therapeutic.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies would evaluate the safety profile of HM43239. As a kinase inhibitor, its potential for off-target effects and associated toxicities would be carefully assessed.
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| Additional Infomation |
Tuspetinib (HM-43239) is currently undergoing clinical trial NCT03850574 (a clinical trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM43239 in patients with relapsed or refractory acute myeloid leukemia). Tuspetinib is a selective, reversible type I FMS-like tyrosine kinase 3 (FLT3; CD135; STK1; FLK2) inhibitor with potential antitumor activity. After administration, tuspetinib reversibly binds to FLT3 and inhibits its activity, thereby inhibiting the proliferation of FLT3-expressing cancer cells. FLT3 is a class III receptor tyrosine kinase (RTK) that is overexpressed or mutated in most B-cell tumors and acute myeloid leukemia.
HM43239 (Tuspetinib) is an investigational drug for the treatment of acute myeloid leukemia (AML). Its ability to inhibit a broad range of FLT3 mutations, including double mutants associated with resistance, positions it as a promising next-generation FLT3 inhibitor. It is an orally active and selective inhibitor of FLT3. |
| Molecular Formula |
C29H33CLN6
|
|---|---|
| Molecular Weight |
501.065524816513
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| Exact Mass |
500.25
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| Elemental Analysis |
C, 69.51; H, 6.64; Cl, 7.07; N, 16.77
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| CAS # |
2569527-64-4
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| Related CAS # |
2758339-04-5 (H2O);2569527-64-4;
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| PubChem CID |
135390910
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| Appearance |
Solid powder
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
725
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H]1CN(C[C@@H](N1)C)CC2=CC(=CC(=C2)NC3=NC=C(C(=N3)C4=CNC5=C4C=CC(=C5)C)Cl)C6CC6
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| InChi Key |
FZLSDZZNPXXBBB-KDURUIRLSA-N
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| InChi Code |
InChI=1S/C29H33ClN6/c1-17-4-7-24-25(12-31-27(24)8-17)28-26(30)13-32-29(35-28)34-23-10-20(9-22(11-23)21-5-6-21)16-36-14-18(2)33-19(3)15-36/h4,7-13,18-19,21,31,33H,5-6,14-16H2,1-3H3,(H,32,34,35)/t18-,19+
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| Chemical Name |
5-chloro-N-[3-cyclopropyl-5-[[(3S,5R)-3,5-dimethylpiperazin-1-yl]methyl]phenyl]-4-(6-methyl-1H-indol-3-yl)pyrimidin-2-amine
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| Synonyms |
HM-43239HM43239 HM 43239
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT03850574
Conditions:Leukemia, Myeloid, Acute|Refractory AML|Relapsed Adult AML|Myelodysplastic Syndrome With Excess Blasts-2|Chronic Myelomonocytic LeukemiaProducts are for research use only; We do not sell to patients
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