受注:045-509-1970 |
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Synonyms | AST-1306 TsOH, AST-6 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C24H18ClFN4O2,C7H8O3S |
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分子量 | 621.08 | CAS No. | 1050500-29-2 | ||||
Solubility (25°C)* | 体外 | DMSO | 124 mg/mL (199.65 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Allitinib (AST-1306, AST-6) is a novel irreversible inhibitor of EGFR and ErbB2 with IC50 of 0.5 nM and 3 nM, also effective in mutation EGFR T790M/L858R, more potent to ErbB2-overexpressing cells, 3000-fold selective for ErbB family than other kinases. |
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in vitro | AST-1306 also ErB2 and EGFR T790M/L858R double mutant. AST-1306 is approximately 500-fold more potent than lapatinib and more than 3000-fold selective for ErbB family kinases over other kinase families including PDGFR, KDR and c-Met. AST-1306 might covalently bind to specific amino acid residues of EGFR and ErbB2. AST-1306 acts in a concentration dependent manner to significantly inhibit the growth of HIH3T3-EGFR T790M/L858R cells. AST-1306 effectively suppresses EGFR phosphorylation in HIH3T3-EGFR T790M/L858R cells. Moreover, AST-1306 blocks the growth of NCI-H1975 cells that harbor the EGFR T790M/L858R mutation in a concentration-dependent manner. AST-1306 blocks phosphorylation of EGFR and downstream pathways as well. In addition, AST-1306 dose-dependently and markedly inhibits EGF-induced EGFR phosphorylation in A549 cells. AST-1306 inhibits the phosphorylation of EGFR and ErbB2, and downstream signaling in human cancer cells including A549 cells, Calu-3 cells and SK-OV-3 cells. [1] |
in vivo | Twice daily oral administration of AST-1306 gives rise to a dramatic prevention of tumor growth in SK-OV-3 and Calu-3 xenograft models. In SK-OV-3 models, tumors nearly disappears after treatment with AST-1306 for 7 days. In contrast, AST-1306 only slightly inhibits the growth of tumor in HO-8910 and A549 xenograft models. Therefore, the antitumor efficacy of AST-1306 is greater in ErbB2-overexpressing tumor models than in models expressing low levels of ErbB2. AST-1306 is well tolerated. Lapatinib displays antitumor activity in these ErbB2-overexpressing tumor models, but AST-1306 is more efficacious than lapatinib in the SK-OV-3 xenograft tumor model when given at the same dose and schedule. In addition, oral administration of AST-1306 twice daily for 3 weeks dramatically suppresses the growth of tumor in the FVB-2/Nneu models. After treatment for 11 days, tumors almost completely disappears. The body weights of the mice reduces by less than 20% during treatment. [1] |
キナーゼアッセイ | Tyrosine kinase assays | |
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The tyrosine kinase activities are determined in 96-well ELISA plates precoated with 20 μg/mL Poly (Glu,Tyr)4:1. First, 80 μL of 5 μM ATP solution diluted in kinase reaction buffer (50 mM HEPES pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2, 0.2 mM Na3VO4, 1 mM DTT) is added to each well. Various concentrations of AST-1306 diluted in 10 μL of 1% DMSO (v/v) are then added to each reaction well, with 1% DMSO (v/v) used as the negative control. Subsequently, the kinase reaction is initiated by the addition of purified tyrosine kinase proteins diluted in 10 μL of kinase reaction buffer solution. Experiments at each concentration are performed in duplicate. After incubation for 60 min at 37 °C, the plate is washed three times with phosphate buffered saline (PBS) containing 0.1% Tween 20 (T-PBS). Next, 100 μL anti-phosphotyrosine antibody (PY99, 1:500 dilution) diluted in T-PBS containing 5 mg/mL BSA is added. After 30 min incubation at 37 °C, the plate is washed three times as before. Horseradish peroxidase-conjugated goat anti-mouse IgG (100 μL) diluted 1:2000 in T-PBS containing 5 mg/mL BSA is added. The plate is reincubated at 37 °C for 30 min, and then washed with PBS. Finally, 100 μL of a solution containing 0.03 % H2O2 and 2 mg/mL o-phenylenediamine in 0.1 M citrate buffer, pH 5.5, is added and samples are incubated at room temperature until color emerged. The reaction is terminated by the addition of 50 μL of 2 M H2SO4, and the plate is read using a multi-well spectrophotometer at 490 nm. The inhibition rate (%) is calculated using the following equation: [1-(A490 treated /A490 control)] ×100%. IC50 values are determined from the results of at least three independent tests and calculated by Logit method. | ||
細胞アッセイ | 細胞株 | Calu-3 and A-549 cell lines |
濃度 | 0.001-1 μM | |
反応時間 | 72 hours | |
実験の流れ | Cell (including Calu-3, A-549 cell line et al.) proliferation is evaluated using the SRB (Sulforhodamine B) assay. Briefly, cells are seeded into 96-well plates and grown for 24 hours. The cells are then treated with increasing concentrations of AST-1306 and grown for a further 72 hours. The medium remains unchanged until the completion of the experiment. The cells are then fixed with 10% precooled trichloroacetic acid (TCA) for 1 hour at 4 °C and stained for 15 min at room temperature with 100 μL of 4 mg/mL SRB solution in 1% acetic acid. The SRB is then removed, and the cells are quickly rinsed five times with 1% acetic acid. After cells are air-dried, protein-bound dye is dissolved in 150 μL of 10 mM Tris base for 5 min and measured at 515 nm using a multiwell spectrophotometer. The inhibition rate on cell proliferation is calculated as (1 - A515 treated/A515 control) × 100%. The IC50 value is obtained by the Logit method and is determined from the results of at least 3 independent tests. | |
動物実験 | 動物モデル | Nude mice bearing SK-OV-3 xenograft tumors and SK-OV-3FVB-2/Nneu transgenic mouse |
投薬量 | 25 mg/kg, 50 mg/kg and 100 mg/kg | |
投与方法 | p.o., twice daily |
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Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line [ Hum Cell, 2024, 10.1007/s13577-024-01054-1] | PubMed: 38565739 |
Epiregulin as an Alternative Ligand for Leptin Receptor Alleviates Glucose Intolerance without Change in Obesity [ Cells, 2022, 11(3)425] | PubMed: 35159237 |
Epiregulin as an Alternative Ligand for Leptin Receptor Alleviates Glucose Intolerance without Change in Obesity [ Cells, 2022, 11(3)425] | PubMed: 35159237 |
Efficacy of Combined Use of Everolimus and Second-Generation Pan-EGRF Inhibitors in KRAS Mutant Non-Small Cell Lung Cancer Cell Lines [ Int J Mol Sci, 2022, 23(14)7774] | PubMed: 35887120 |
High ErbB3 Activating Activity in Human Blood Is Not Due to Circulating neuregulin-1 Beta [ Life Sci, 2020, 15;251:117634] | PubMed: 32251632 |
Betacellulin-Induced α-Cell Proliferation Is Mediated by ErbB3 and ErbB4, and May Contribute to β-Cell Regeneration [ Front Cell Dev Biol, 2020, 8:605110] | PubMed: 33553143 |
Betacellulin enhances ovarian cancer cell migration by up-regulating Connexin43 via MEK-ERK signaling. [ Cell Signal, 2020, 65:109439] | PubMed: 31654720 |
Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors. [ Cell Rep, 2019, 28(9):2331-2344] | PubMed: 31461650 |
LncRNA AFAP1-AS1 Supresses miR-139-5p and Promotes Cell Proliferation and Chemotherapy Resistance of Non-small Cell Lung Cancer by Competitively Upregulating RRM2 [ Front Oncol, 2019, 9:1103] | PubMed: 31696057 |
ErbB2 promotes endothelial phenotype of human left ventricular epicardial highly proliferative cells (eHiPC) [Ryzhov S J Mol Cell Cardiol, 2018, 115:39-50] | PubMed: 29291395 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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