ATH686 is a novel and selective FLT3 Inhibitor. ATH686 is part of a novel class of extremely powerful FLT3 inhibitors that can overcome drug resistance in a way that less powerful "type I" and "type II" first-generation FLT3 inhibitors are unable to.
Physicochemical Properties
| Molecular Formula | C25H28F3N7O2 |
| Molecular Weight | 515.5412 |
| Exact Mass | 515.226 |
| Elemental Analysis | C, 58.24; H, 5.47; F, 11.06; N, 19.02; O, 6.21 |
| CAS # | 853299-52-2 |
| Related CAS # | 853299-52-2 |
| PubChem CID | 11477833 |
| Appearance | White to light brown solid powder |
| LogP | 5.254 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 37 |
| Complexity | 715 |
| Defined Atom Stereocenter Count | 0 |
| 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 |
| InChi Key | VQQRBBFRJRBWPF-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 1-[4-(2-aminopyrimidin-4-yl)oxyphenyl]-3-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea |
| Synonyms | ATH 686; ATH686; ATH-686 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| 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. |
| References |
[1]. Antileukemic Effects of Novel First- and Second-Generation FLT3 Inhibitors: Structure-Affinity Comparison. Genes Cancer. 2010 Oct;1(10):1021-32. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~250 mg/mL (~484.9 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |