Allitinib tosylate

SKU: orb1300862

Description

Allitinib tosylate (AST-1306) is a potent, irreversible small molecule inhibitor targeting EGFR and ErbB2, with respective IC50 values of 0.5 nM and 3 nM. It is utilized in cancer research for in vitro and in vivo studies, particularly in investigating resistance mechanisms in non-small cell lung and breast cancers.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1050500-29-2
• MW: 621.08
• Purity: 98.68%
• Formula: C₃₁H₂₆ClFN₄O₅S
• SMILES: Cc1ccc(cc1)S(O)(=O)=O.Fc1cccc(COc2ccc(Nc3ncnc4ccc(NC(=O)C=C)cc34)cc2Cl)c1
• Target: EGFR,FLT
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (6.44 mM);DMSO:114 mg/mL (183.55 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  EGFR L858R/T790M:12 nM|ERB4:0.8 nM|ErbB2:3.0 nM|EGFR:0.5 nM
• In Vivo:
  Twice daily oral administration of Allitinibgives 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 Allitinibfor 7 days. In contrast, Allitinibonly slightly inhibits the growth of tumor in HO-8910 and A549 xenograft models. Therefore, the antitumor efficacy of Allitinibis greater in ErbB2-overexpressing tumor models than in models expressing low levels of ErbB2. Allitinibis well tolerated. Lapatinib displays antitumor activity in these ErbB2-overexpressing tumor models, but Allitinibis 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 Allitinibtwice 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.
• In Vitro:
  Allitinibalso ErB2 and EGFR T790M/L858R double mutant. Allitinibis 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. Allitinibmight covalently bind to specific amino acid residues of EGFR and ErbB2. Allitinibacts in a concentration dependent manner to significantly inhibit the growth of HIH3T3-EGFR T790M/L858R cells. Allitinibeffectively suppresses EGFR phosphorylation in HIH3T3-EGFR T790M/L858R cells. Moreover, Allitinibblocks the growth of NCI-H1975 cells that harbor the EGFR T790M/L858R mutation in a concentration-dependent manner. Allitinibblocks phosphorylation of EGFR and downstream pathways as well. In addition, Allitinibdose-dependently and markedly inhibits EGF-induced EGFR phosphorylation in A549 cells. Allitinibinhibits the phosphorylation of EGFR and ErbB2, and downstream signaling in human cancer cells including A549 cells, Calu-3 cells and SK-OV-3 cells.
• Cell Research:
  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.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

HER2/ErbB2, FLT1, EGFR, EGFR (T790M/L858R), AST 1306, AST6, AST 6, AST1306, AST-1306 (TsOH), AST-1306 TsOH, anilino-quinazoline, TsOH

Compound Identifiers

PubChem CID

25027665