| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
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| ln Vitro |
In BCRABL-driven cancer cell lines, CHMFL-ABL-039 (0-10 μM; 72 hr) is 6–10 times more sensitive than imatinib and is BCR–ABL independent. The cell lines also exhibit strong selectivity windows. There is no overall cytotoxicity shown by CHMFL-ABL-039 [1]. ABL Y245 phosphorylation and the ensuing downstream signaling mediators are dose-dependently inhibited by CHMFL-ABL-039 (0.01-3 μM; 4 hours) [1]. detection of cell proliferation [1]
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| ln Vivo |
CHMFL-ABL-039 (25-100 mg/kg; i.p.; daily for 28 days in a K562-mediated five-week-old female nu/nu mouse model, and five weeks in a BaF3-BCR-ABL-V299L-mediated nu/nu mouse model) did not demonstrate any obvious general toxicity and did not influence mouse body weight. CHMFL-ABL-039 dose-dependently reduced tumor progression in both models at any dose [1].
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| Cell Assay |
Cell proliferation detection [1]
Cell Types: K562, KU812, MEG-01 (BCRABL driven cancer cell lines); HL-60, MOLM-14, MV4-11, U937 (BCR-ABL independent cell lines); CD34+ (normal cells) Tested Concentrations: 0-10 μM Incubation Duration: 72 hrs (hours) Experimental Results: 6-10-fold increased sensitivity to BCRABL-driven cancer cell lines including K562, KU812, and MEG01 compared to imatinib. HL-60, MOLM-14, MV4-11, and U937 demonstrated good selectivity windows compared to BCR-ABL driven cell lines. CHMFL-ABL-039 demonstrated a similar range of antiproliferative effects on CD34+ cells, suggesting the absence of general cytotoxicity. Western Blot Analysis[1] Cell Types: BaF3-BCR-ABL-V299L cells, KU812 cells, MEG-01 cells, K562 cells Tested Concentrations: 0.01 μM, 0.03 μM, 0.1 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM Incubation Duration: 4 hrs (hours) Experimental Results: Dose-dependent inhibition of ABL Y245 phosphorylation and subsequent downstream signaling mediators such as pSTAT5 Y694, pERK T202/204 in K562, KU812, MEG-01 and BaF3-BCR-ABL-V299L. |
| Animal Protocol |
Animal/Disease Models: BaF3-BCR-ABL-V299L (imatinib insensitive) and K562 cell inoculated xenograft mouse model (fiveweeks old female nu/nu (nude) mice) [1]
Doses: 25 mg/kg, 50 mg /kg, 100 mg/kg Route of Administration: ipinjection; one time/day for 28 days (K562-mediated model), one time/day for 11 days (BaF3-BCR-ABL-V299L-mediated model) Experimental Results: No manifestations Any general toxicity was apparent and mouse body weight was not affected. Both models dose-dependently inhibited tumor progression at doses of 25, 50, and 100 mg/kg. In the K562-mediated model, daily administration of CHMFL-ABL-039 at 25 mg/kg achieved 77% tumor growth inhibition (TGI) and even almost complete tumor elimination (TGI: approximately 100%) at the 100 mg/kg dose. In an imatinib-insensitive BaF3-BCR-ABL-V299L mutant cell-mediated xenograft model, a dose of 25 mg/kg of CHMFL-ABL-039 demonstrated similar efficacy to 100 mg/kg. |
| References |
| Molecular Formula |
C31H33F3N6O3
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|---|---|
| Molecular Weight |
594.627337217331
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| Exact Mass |
594.256
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| CAS # |
2304344-56-5
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| PubChem CID |
138377598
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
43
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| Complexity |
963
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RBWVZGKOJYNSAN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H33F3N6O3/c1-39-12-14-40(15-13-39)19-23-7-6-22(17-26(23)31(32,33)34)30(43)37-24-8-2-20(3-9-24)16-28(41)36-25-10-11-27(35-18-25)38-29(42)21-4-5-21/h2-3,6-11,17-18,21H,4-5,12-16,19H2,1H3,(H,36,41)(H,37,43)(H,35,38,42)
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| Chemical Name |
N-[4-[2-[[6-(cyclopropanecarbonylamino)pyridin-3-yl]amino]-2-oxoethyl]phenyl]-4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzamide
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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 | 1.6817 mL | 8.4086 mL | 16.8172 mL | |
| 5 mM | 0.3363 mL | 1.6817 mL | 3.3634 mL | |
| 10 mM | 0.1682 mL | 0.8409 mL | 1.6817 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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