| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
BLU-654 effectively inhibited the autophosphorylation of KIT in HMC1.1 11/13 cells with an IC50 value of 5.7 nM[1]. BLU-654 inhibited the autophosphorylation of wild-type KIT in M-07e cells with an IC50 value of 82.7 nM, and its selectivity for KITV654A was 15 times higher than that for wild-type KIT[1]. BLU-654 inhibited the autophosphorylation of PDGFRβ in SW569 cells with an IC50 value of 1251.4 nM, and its selectivity for KITV654A was 219 times higher than that for PDGFRβ[1]. BLU-654 exhibited species-dependent metabolic stability, with no inherent clearance in human and canine liver microsomes, low clearance in human hepatocytes (2 mL·min-1·kg-1), and high clearance in rat, canine, and cynomolgus monkey hepatocytes[1].
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|---|---|
| ln Vivo |
BLU-654 (1-60 mg/kg; orally; once daily; 27 days) showed potent dose-dependent inhibition of pSTAT5 (a downstream marker of KIT activity) in HMC1.1 11/13 xenografts [1].
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| Animal Protocol |
Animal/Disease Models:NOD-SCID Mice [1]
Doses: 1-30 mg/kg (pharmacokinetics/pharmacodynamics); 3-60 mg/kg (efficacy) Route of Administration: Oral; Daily; 27 days (efficacy); Single Dosage (pharmacokinetics/pharmacodynamics) Experimental Results: Dose- and time-dependent reduction of pSTAT5 was observed, with a free IC50 of 4.2 nM at 4 hours. At a dose of 10 mg/kg, pSTAT5 decreased by 95% within 4 hours and recovered to 68% of baseline levels after 24 hours. Within 10 hours after administration, plasma drug concentrations in most dose groups reached dose-dependent levels, exceeding the in vitro pKIT IC50 value; in the 30 mg/kg dose group, plasma drug concentrations remained higher than the in vitro IC50 value for up to 24 hours. After 27 days of daily administration, tumor growth was slower in the 3 mg/kg dose group compared to the control group. Tumors were eliminated in the 10, 30, and 60 mg/kg dose groups, and no tumor recurrence was observed during the 48-day post-treatment observation period. The body weight of mice in all dose groups remained within 10% of baseline, indicating good tolerability of the drug. |
| References |
| Molecular Formula |
C21H28FN7O2
|
|---|---|
| Molecular Weight |
429.49
|
| CAS # |
2999638-62-7
|
| Appearance |
Typically exists as solids at room temperature
|
| SMILES |
F[C@@H](C)C1=NC(N)=CC(NC2=NC=C(C3=CN(CC(C)(O)C)N=C3)C(OC(C)C)=C2)=N1
|
| 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)
|
| 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 | 2.3283 mL | 11.6417 mL | 23.2834 mL | |
| 5 mM | 0.4657 mL | 2.3283 mL | 4.6567 mL | |
| 10 mM | 0.2328 mL | 1.1642 mL | 2.3283 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.
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