Brief Description

R428 is a potent and selective small-molecule inhibitor(IC50=14 nM), blocks the activities of Axl.
IC50 value: 14 nM
Target: Axl kinase
in vitro: R428 exhibited potent activity (EC50/IC50, 14 nmol/L) in both in vitro biochemical kinase assays using recombinant Axl protein and a cell-based assay reflecting Axl signaling in HeLa cells that uses downstream phosphorylation of Akt on Ser473 as the readout. R428 potently blocked autophosphorylation on a COOH-terminal multiple docking site, Tyr821, stimulated by either antibody-mediated cross-linking or Gas6. Pharmacological inhibition of Axl with R428 in EAC cell lines significantly reduced anchorage-independent growth, invasion and migration.
in vivo: Pharmacologic investigations revealed favorable exposure after oral administration such that R428-treated tumors displayed a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. In a recent study, the Axl inhibitor R428 shows a mean IC50 dose of 2.0μM for the primary CLL B cells after 24 hours of treatment and normal B-, T-, and natural killer (NK) cells show no significant amount of cell death at this dose of R428 (2.5 μM) under similar experimental conditions. R428 inhibits angiogenesis in corneal micropocket and tumor models.

Solubility

DMSO > 100 mg/ml

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid