R428

Bezeichnung:R428

CAS-Nr1037624-75-1

Englisch Name:R428

CBNumberCB42621146

SummenformelC30H34N8

Molgewicht506.64

MOL-Datei1037624-75-1.mol

R428 physikalisch-chemischer Eigenschaften

Schmelzpunkt	>211°C (dec.)
Siedepunkt	799.6±70.0 °C(Predicted)
Dichte	1.41±0.1 g/cm3(Predicted)
storage temp.	-20°C
Löslichkeit	Soluble in DMSO (up to at least 25 mg/ml)
Aggregatzustand	Yellow powder.
pka	10.34±0.20(Predicted)
Farbe	Yellow
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

Gefahreninformationscode (GHS)

R428 Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
R428 (bemcentinib, BGB324), a selective small-molecule inhibitor of AXL, is currently being evaluated in phase II trials for the treatment of non-small-cell lung cancer (NSCLC) and acute myelocytic leukemia (AML). It has been found to induce apoptosis in cancer cells and to block tumor spread in models of metastatic breast cancer. The therapeutic potential of R428 has also been demonstrated in highly invasive esophageal adenocarcinoma cells and in ESCC cells.
R428 is a selective, small molecule inhibitor of Axl that blocks its catalytic and precancerous activities. R428 treatment reduced Axl-induced AKT phosphorylation, cancer cell invasion, angiogenesis, and the production of pro-inflammatory cytokines. It also reduced the expression of the cytokine granulocyte macrophage colony-stimulating factor and Snail in a dosage-dependent manner. Interestingly,using R428 to inhibit Axl-mediated cellular and molecular functions during cisplatin treatments achieved an enhanced suppression of liver metastases. Axl knockdowns in RAC cell lines reduced migration, invasion, and in vivo engraftment, accompanied by a downregulation in the activity of the Ral GTPase proteins (RalA and RalB). Similar effects were obtained using an A428 inhibitor. Blocking Axl functions also abrogated the phosphorylation of ERBB2 (Her-2/neu) at the Tyr877 residue, which reveals the cross-functional effects of R428 on different receptor signaling axes.
Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)
Verwenden
R 428 is an AXL tyrosine kinase inhibitor shown to be used as an anti-cancer agent.
target
Axl
Einzelnachweise
1) Holland?et al.?(2010),?R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer;?Cancer Res.?70?1544 2) Fleuren?et al.?(2014),?The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma;?Oncotarget?5?12753 3) Xu?et al.?(2014),?Inhibition of Axl improves the targeted therapy against ALK-mutated neuroblastoma;?Biochem. Biophys. Res. Commun.?454?566 4) Ben-Batalla?et al.?(2017),?Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor-Sensitive and -Resistant Chronic Myeloid Leukemia;?Clin. Cancer Res.?23?2289 5) Lin?et al.?(2017),?Targeting AXL overcomes resistance to docetaxel therapy in advanced prostate cancer;?Oncotarget?8?41064 6) Guo?et al.?(2017),?Axl inhibition induces the antitumor immune response which can be further potentiated by PD-1 blockade in the mouse cancer models;?Oncotarget?8?89761 7) Ludwig?et al.?(2018),?Small-Molecule Inhibition of Axl Targets Tumor Immune

R428 Upstream-Materialien And Downstream Produkte

R428 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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