| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
The primary target is the c-KIT T670I mutant kinase, a gain-of-function mutation that confers resistance to imatinib in GISTs. CHMFL-KIT-033 is a type II kinase inhibitor that binds to the inactive conformation of c-KIT T670I, blocking its autophosphorylation and downstream signaling (e.g., MAPK/ERK, PI3K/AKT). It shows 12-fold selectivity over wild-type c-KIT, which is important for minimizing toxicity related to wild-type KIT inhibition in hematopoiesis.
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| ln Vitro |
CHMFL-KIT-033 is a potent and selective inhibitor of c-KIT T670I with an IC50 of 0.045 µM. It shows good antiproliferative effects against c-KIT T670I mutant-driven GIST cell lines (GIST-T1/T670I and GIST-5R). The compound exhibits 12-fold selectivity for the mutant over wild-type c-KIT. It displays suitable in vivo pharmacokinetic profiles and dose-dependent antitumor efficacy in mouse xenograft models.
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| ln Vivo |
In vivo, CHMFL-KIT-033 exhibits dose-dependent antitumor efficacy in a GIST-5R mouse xenograft model. The compound shows favorable pharmacokinetic properties and is orally bioavailable. Dose-dependent tumor growth inhibition is observed. The compound demonstrates confirmed in vivo efficacy in GIST-5R xenograft models, establishing it as a valuable tool for studying mutant-selective kinase pharmacology. Typical doses range from 10-100 mg/kg administered orally.
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| Enzyme Assay |
Kinase activity assays use recombinant c-KIT T670I or wild-type c-KIT kinase domains and a poly(Glu,Tyr) 4:1 substrate. CHMFL-KIT-033 is incubated with the kinase and substrate in assay buffer containing ATP. Phosphorylation is measured by ELISA or scintillation counting. IC50 values are calculated from dose-response curves. Selectivity is profiled using the KINOMEscan™ platform.
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| Cell Assay |
Cell-based assays use GIST-T1/T670I and GIST-5R cell lines cultured in RPMI-1640 with serum. Cells are treated with CHMFL-KIT-033 (0.001-10 µM) for 72 hours. Cell viability is measured by MTT or SRB assay. c-KIT phosphorylation and downstream signaling (p-ERK, p-AKT) are measured by Western blotting. Apoptosis is assessed by caspase-3 activation.
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| Animal Protocol |
In vivo, CHMFL-KIT-033 is tested in mouse xenograft models. A typical protocol involves subcutaneous inoculation of GIST-5R cells into female athymic nude mice (4-6 weeks old). When tumors reach ~100-200 mm³, mice are treated with CHMFL-KIT-033 formulated in 0.5% carboxymethylcellulose with 0.1% Tween 80 in sterile water, administered orally. Tumor volume is measured, and dose-dependent tumor growth inhibition is assessed.
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| References |
| Molecular Formula |
C23H18FN5O2
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|---|---|
| Molecular Weight |
415.42
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| Exact Mass |
415.144
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| CAS # |
2351801-41-5
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| PubChem CID |
138454794
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| Appearance |
Light yellow to yellow solid
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| Density |
1.451±0.06 g/cm3(Predicted)
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| Boiling Point |
772.4±60.0 °C(Predicted)
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| LogP |
4.2
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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 |
31
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| Complexity |
660
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC1=CC=CC(F)=C1)(=O)CC(NC1=CC2=C(C=C1)C(/C=C/C1=NC=CC=C1)=NN2)=O
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| InChi Key |
OLZDZYHEIBZXCI-CSKARUKUSA-N
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| InChi Code |
InChI=1S/C23H18FN5O2/c24-15-4-3-6-17(12-15)26-22(30)14-23(31)27-18-7-9-19-20(28-29-21(19)13-18)10-8-16-5-1-2-11-25-16/h1-13H,14H2,(H,26,30)(H,27,31)(H,28,29)/b10-8+
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| Chemical Name |
N-(3-fluorophenyl)-N'-[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]propanediamide
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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) |
DMSO: ~100 mg/mL (~240.7 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (12.04 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (12.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4072 mL | 12.0360 mL | 24.0720 mL | |
| 5 mM | 0.4814 mL | 2.4072 mL | 4.8144 mL | |
| 10 mM | 0.2407 mL | 1.2036 mL | 2.4072 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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