| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
ATH686 targets FMS-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase involved in hematopoiesis. It is a selective inhibitor of mutant FLT3 protein kinase activity. The compound is ATP-competitive and belongs to a second-generation class of FLT3 inhibitors that can overcome drug resistance. ATH686 selectively kills leukemic cells harboring mutant FLT3 with no apparent effect on cells harboring wild-type FLT3. This selectivity is an important feature for its antileukemic activity.
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| ln Vitro |
ATH686 (1-100 µM; 3 days) induces apoptosis in FLT3-ITD-Ba/F3 and D835Y-Ba/F3 cells, thereby potently inhibiting cell proliferation (IC50 approximately 0.001 µM)[1].
ATH686 (10 nM) inhibits the autophosphorylation of mutant FLT3 for a duration of 15 minutes in FLT3-ITD-Ba/F3 cells[1]. In vitro, ATH686 potently inhibits cell proliferation in FLT3-mutant cell lines. In FLT3-ITD-Ba/F3 cells and D835Y-Ba/F3 cells, ATH686 (1-100 µM; 3 days) potently inhibits cell proliferation with an IC50 around 0.001 µM via induction of apoptosis. It selectively kills leukemic cells harboring mutant FLT3 with no apparent effect on cells harboring wild-type FLT3. These in vitro activities demonstrate its potent and selective antileukemic effects against FLT3-mutant cells. |
| ln Vivo |
In vivo, ATH686 has been studied in preclinical models of leukemia. It inhibits the proliferation of cells harboring FLT3 mutations and has antileukemic effects. The compound's ability to overcome drug resistance is a key feature, as it can inhibit mutant FLT3 that is resistant to first-generation inhibitors. However, specific details of in vivo studies, such as the animal models used and the dosing regimens, are not extensively detailed in the available literature.
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| Enzyme Assay |
The in vitro kinase assay for ATH686 typically measures its ability to inhibit FLT3 kinase activity. These cell-free assays use purified recombinant FLT3 enzyme and a peptide substrate in the presence of ATP. The compound's inhibitory potency (IC50) is determined by measuring the reduction in kinase activity, often using radioactive or fluorescence-based detection methods. These assays allow for the direct assessment of the compound's potency against FLT3 and its selectivity over other kinases.
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| Cell Assay |
Cell Line: FLT3-ITD-Ba/F3 cells and D835Y-Ba/F3 cells
Concentration: 1, 5, 10, 50, 100 µM Incubation Time: 3 days Result: Potently inhibited cell proliferation (IC50 around 0.001 µM) via induction of apoptosis. In vitro cellular assays for ATH686 assess its antiproliferative and pro-apoptotic effects in FLT3-mutant cell lines. Cells such as FLT3-ITD-Ba/F3 and D835Y-Ba/F3 are treated with various concentrations of the compound for 3 days. Cell proliferation is measured using assays such as MTT or CellTiter-Glo. Apoptosis is assessed using Annexin V/PI staining or by measuring caspase activation. Cell cycle analysis is performed using flow cytometry. These assays demonstrate the compound's ability to inhibit proliferation and induce apoptosis in FLT3-mutant cells. |
| Animal Protocol |
In vivo animal studies for ATH686 are not extensively detailed in the available literature. However, as a preclinical candidate for leukemia, the compound would have been evaluated in mouse xenograft models using FLT3-mutant leukemic cell lines. In these studies, immunodeficient mice are implanted with tumor cells, and after tumor establishment, ATH686 is administered. Tumor growth is monitored, and endpoints such as tumor volume, survival, and assessment of apoptosis in tumor tissues are measured. These studies would demonstrate the compound's in vivo antileukemic efficacy.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for ATH686 are not extensively detailed in the available literature. As a small molecule inhibitor, its pharmacokinetic properties would be typical of this class of compounds. The compound's oral bioavailability, half-life, and distribution would be important for its in vivo efficacy. However, without specific data, a detailed pharmacokinetic profile cannot be provided. The compound's ability to target FLT3-mutant cells in vivo would depend on its pharmacokinetic properties.
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| Toxicity/Toxicokinetics |
Specific toxicity data for ATH686 are not extensively detailed in the available literature. As a selective FLT3 inhibitor, its toxicity profile is likely related to its mechanism of action, potentially affecting normal hematopoietic cells that depend on FLT3 signaling. However, the compound's selectivity for mutant over wild-type FLT3 may contribute to a favorable safety profile. Preclinical toxicology studies would typically be conducted to assess the compound's safety margin, but these specific data are not provided.
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| References | |
| Additional Infomation |
ATH686 is a potent and selective second-generation FLT3 inhibitor that has been developed as a potential therapeutic agent for acute myeloid leukemia (AML) harboring FLT3 mutations. Its key feature is its ability to overcome drug resistance that limits the efficacy of first-generation FLT3 inhibitors. The compound selectively targets mutant FLT3 with no apparent effect on wild-type FLT3. It is a research compound and is not approved for clinical use. It is intended for research purposes only.
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| Molecular Formula |
C25H28F3N7O2
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|---|---|
| Molecular Weight |
515.5412
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| Exact Mass |
515.226
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| Elemental Analysis |
C, 58.24; H, 5.47; F, 11.06; N, 19.02; O, 6.21
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| CAS # |
853299-52-2
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| Related CAS # |
853299-52-2
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| PubChem CID |
11477833
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| Appearance |
White to light brown solid powder
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| LogP |
5.254
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
37
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| Complexity |
715
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NC1C=C(C(F)(F)F)C(CN2CCN(CC)CC2)=CC=1)NC1C=CC(OC2C=CN=C(N)N=2)=CC=1
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| InChi Key |
VQQRBBFRJRBWPF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H28F3N7O2/c1-2-34-11-13-35(14-12-34)16-17-3-4-19(15-21(17)25(26,27)28)32-24(36)31-18-5-7-20(8-6-18)37-22-9-10-30-23(29)33-22/h3-10,15H,2,11-14,16H2,1H3,(H2,29,30,33)(H2,31,32,36)
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| Chemical Name |
1-[4-(2-aminopyrimidin-4-yl)oxyphenyl]-3-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea
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| Synonyms |
ATH 686; ATH686; ATH-686
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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: ~250 mg/mL (~484.9 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: ≥ 2.08 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9397 mL | 9.6986 mL | 19.3971 mL | |
| 5 mM | 0.3879 mL | 1.9397 mL | 3.8794 mL | |
| 10 mM | 0.1940 mL | 0.9699 mL | 1.9397 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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