product name R428 (BGB324)
Description: R428 (also known as BGB324) is a potent and selective inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. The selectivty of R428 for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective). R428 showed activity to blocks tumor spread and prolongs survival in models of metastatic breast cancer.
References: Cancer Res. 2010 Feb 15;70(4):1544-54; Blood. 2011 Feb 10;117(6):1928-37.
506.64
Formula
C30H34N8
CAS No.
1037624-75-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 6 mg/mL (11.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
5% DMSO+corn oil: 1 mg/mL
Synonyms
BGB324
other peoduct :
| In Vitro |
In vitro activity: R428 blocks the catalytic and procancerous activities of Axl. R428 inhibits Axl with low nanomolar activity and blocks 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. Kinase Assay: Cell Assay: R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. |
|---|---|
| In Vivo | Pharmacologic investigations reveal favorable exposure after oral administration such that R428-treated tumors display a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. In support of an earlier study, R428 inhibits angiogenesis in corneal micropocket and tumor models. R428 administration reduces metastatic burden and extends survival in MDA-MB-231 intracardiac and 4T1 orthotopic (median survival, >80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis. |
| Animal model | MDA-MB-231-luc-D3H2LN Intracardiac Model |
| Formulation & Dosage | Dissolved in 0.5% hydroxypropylmethylcellulose + 0.1% Tween 80; 125 mg/kg; Oral gavage |
| References | Cancer Res. 2010 Feb 15;70(4):1544-54; Blood. 2011 Feb 10;117(6):1928-37. |
