Allitinib tosylate
(formerly AST-1306; AST1306; AST 1306), the tosylate of Allitinib, is a selective and covalent/irreversible inhibitor of EGFR and ErbB2 with
potential anticancer activity.
Physicochemical Properties
| Molecular Formula | C₃₁H₂₆CLFN₄O₅S |
| Molecular Weight | 621.08 |
| Exact Mass | 620.129 |
| CAS # | 1050500-29-2 |
| Related CAS # | Allitinib;897383-62-9 |
| PubChem CID | 25027665 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 8.914 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 43 |
| Complexity | 848 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ZMUKJEHWLJBODV-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C24H18ClFN4O2.C7H8O3S/c1-2-23(31)29-17-6-8-21-19(11-17)24(28-14-27-21)30-18-7-9-22(20(25)12-18)32-13-15-4-3-5-16(26)10-15;1-6-2-4-7(5-3-6)11(8,9)10/h2-12,14H,1,13H2,(H,29,31)(H,27,28,30);2-5H,1H3,(H,8,9,10) |
| Chemical Name | N-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]prop-2-enamide;4-methylbenzenesulfonic acid |
| Synonyms | AST-1306 AST 1306AST1306 |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | On the development of HIH3T3-EGFR T790M/L858R cells, AST1306 tosylate (AST-1306 (TsOH); 0.19-6.25 μM; 72 hours) can have notable, concentration-dependent inhibitory effects [1]. In A549 cells, Calu-3 cells, and SK-OV-3 cells, AST1306 tosylate suppresses the activation of tyrosine kinases and downstream signaling pathways. In A549 cells, AST1306 tosylates in a dose-dependent manner and notably prevents EGF-induced EGFR phosphorylation [1]. Two tumor cells grown on soft agar can be significantly inhibited by AST1306 tosylate (0.1, 0.5, 1.0, 5.0 μM), with SK-OV-3 cells exhibiting far higher sensitivity than A549 cells [1]. Compared to other kinase families, AST1306 tosylate (0.001-1.0 μM; 4 hours) is more than 3000 times more selective for ErbB family kinases [1]. With an IC50 value of 12±2 nmol/L, AST1306 tosylate efficiently suppresses the EGFR T790M/L858R double mutant[1]. |
| ln Vivo | Tumor growth in SK-OV-3 and Calu-3 xenograft models is significantly inhibited by AST1306 tosylate (AST-1306 (TsOH); oral; 25–100 mg/kg; twice daily; for 28 days [1]. |
| Cell Assay |
Cell Proliferation Assay [1] Cell Types: NIH3T3 Parental and NIH3T3 Cell Tested Concentrations: 0.19, 0.39, 0.78, 1.56, 3.13, 6.25 μM Incubation Duration: 72 hrs (hours) Experimental Results: Significant concentration-dependent inhibition of EGFR on the growth of HIH3T3- T790M/L858R cells. Western Blot Analysis[1] Cell Types: A549 cells, Calu-3 cells and SK-OV-3 cells Tested Concentrations: 0.001, 0.01, 0.1, 1.0 μM Incubation Duration: 4 hrs (hours) Experimental Results: Inhibition of tyrosine kinases and downstream signaling pathways activation. |
| Animal Protocol |
Animal/Disease Models: SK-OV-3 and Calu-3 tumor nude mice [1] Doses: 25, 50, 100 mg/kg Route of Administration: po (po (oral gavage)) twice a day; lasted for 28 days. Experimental Results: Dramatically inhibited tumor growth. |
| References |
[1]. AST1306, a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, exhibits antitumor activity both in vitro and in vivo. PLoS One. 2011;6(7):e21487. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~80.50 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.03 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6101 mL | 8.0505 mL | 16.1010 mL | |
| 5 mM | 0.3220 mL | 1.6101 mL | 3.2202 mL | |
| 10 mM | 0.1610 mL | 0.8050 mL | 1.6101 mL |