1037624-75-1 Usage
Description
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)
Uses
R 428 is an AXL tyrosine kinase inhibitor shown to be used as an anti-cancer agent.
References
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
Check Digit Verification of cas no
The CAS Registry Mumber 1037624-75-1 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,3,7,6,2 and 4 respectively; the second part has 2 digits, 7 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 1037624-75:
(9*1)+(8*0)+(7*3)+(6*7)+(5*6)+(4*2)+(3*4)+(2*7)+(1*5)=141
141 % 10 = 1
So 1037624-75-1 is a valid CAS Registry Number.
1037624-75-1Relevant articles and documents
Bemcentinib: Rec INN
Gras
, p. 645 - 653 (2018/10/20)
Increased expression of Axl has been reported in various cancers including colon, esophageal, thyroid, breast, lung, liver and astrocytoma-glioblastoma. Cancer resistance to tyrosine kinase inhibitors and other chemotherapeutics has been correlated with a
POLYCYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS
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Page/Page column 144, (2008/12/07)
Polycyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases
