AST-1306 Chemical Properties

Boiling point:

655℃

Density 

1.395

Flash point:

350℃

storage temp. 

Store at -20°C

solubility 

≥22.45 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH

form 

solid

pka

12.16±0.43(Predicted)

color 

White to off-white

InChIKey

MVZGYPSXNDCANY-UHFFFAOYSA-N

SMILES

C(NC1C=CC2C(C=1)=C(NC1=CC=C(OCC3=CC=CC(F)=C3)C(Cl)=C1)N=CN=2)(=O)C=C

AST-1306 Usage And Synthesis

Uses

AST-1306 is a novel irreversible inhibitor of EGFR and ErbB4 with IC50 of 0.5 nM and 0.8 nM, respectively.

Uses

AST-1306 is a selective irreversible inhibitor of the epidermal growth factor receptor (EGFR) 1 and 2. Studies show that AST-1306 inhibited the enzymatic activities of wild-type EGF) and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. AST-1306 was more effective in inhibiting tumors with ErbB2-overexpressing cells than EGFR-overexpressing tumor.

Definition

ChEBI: N-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-quinazolinyl]-2-propenamide is a member of quinazolines.

Biological Activity

ast1306 is a novel inhibitor of egfr and her2 (ic50 = 0.5 nm and 3 nm respectively)egfr (epidermal growth factor receptor) is a cell-surface receptor tyrosine kinase. the receptor activation leads to dimerization and tyrosine autophosphorylation. it induces a cascade of downstream cellular responses such as modification in gene expression, cell proliferation and cytoskeletal rearrangement etc. her2 is a member of the epidermal growth factor and is associated with breast and ovarian cancers.ast1306 selectively blocked egfr and her2 kinase activities in a cell-free assay. the tyrosine kinase activity of egfr mutant t790m/l858r was also inhibited by ast1306 in intact cell and cell-free assays. in addition, ast1306 attenuated the egfr and her2 phosphorylation and downstream substrates. [1]in erbb2-overexpressing xenograft and fvb-2/nneu transgenic mouse model, ast1306 potently inhibited tumor growth. in sk-ov-3 xenograft model, ast1306 caused a quick and long-lasting (≥24h) inhibition of egfr and her2. [1]

in vivo

IC 50

EGFR: 0.5 nM (IC₅₀); EGFR^L858R/T790M: 12 nM (IC₅₀); ErbB2: 3 nM (IC₅₀); ErbB4: 0.8 nM (IC₅₀)

References

1. xie h, lin l, tong l et al. 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.