1037624-75-1 Usage
Description
R428, also known as bemcentinib or BGB324, is a selective small-molecule inhibitor of AXL tyrosine kinase. It is currently under evaluation in phase II trials for the treatment of non-small-cell lung cancer (NSCLC) and acute myelocytic leukemia (AML). R428 has demonstrated the ability to induce apoptosis in cancer cells, block tumor spread, and reduce Axl-induced AKT phosphorylation, cancer cell invasion, angiogenesis, and the production of pro-inflammatory cytokines.
Uses
Used in Anticancer Applications:
R428 is used as an anti-cancer agent for its ability to inhibit AXL tyrosine kinase, which plays a role in cancer cell growth, survival, and metastasis. It has shown potential in the treatment of non-small-cell lung cancer (NSCLC) and acute myelocytic leukemia (AML) by inducing apoptosis in cancer cells and blocking tumor spread.
Used in Drug Delivery Systems:
R428 is used in drug delivery systems to enhance its applications and efficacy against cancer cells. By employing various organic and metallic nanoparticles as carriers for R428 delivery, its bioavailability and therapeutic outcomes can be improved.
Used in Combination Therapies:
R428 is used in combination therapies with conventional chemotherapeutic drugs, such as cisplatin, to enhance chemo-sensitivity and efficacy in resistant cases. It has been shown to achieve an enhanced suppression of liver metastases when used in conjunction with cisplatin treatments.
Used in Targeting Specific Cancer Types:
R428 is used as a targeted therapy for various cancer types, including highly invasive esophageal adenocarcinoma cells and esophageal squamous cell carcinoma (ESCC). It has demonstrated the ability to reduce cancer cell invasion, angiogenesis, and the production of pro-inflammatory cytokines, as well as to block the phosphorylation of ERBB2 (Her-2/neu) at the Tyr877 residue, revealing its cross-functional effects on different receptor signaling axes.
Used in Inhibiting AXL-Mediated Cellular Functions:
R428 is used to inhibit Axl-mediated cellular and molecular functions, which can lead to reduced migration, invasion, and in vivo engraftment of cancer cells. It also results in a downregulation in the activity of the Ral GTPase proteins (RalA and RalB), further contributing to its anti-cancer properties.
Used in Combination with Other Inhibitors:
R428 is used in combination with other inhibitors, such as cabozantinib (XL184), to inhibit the growth of esophageal squamous cell carcinoma (ESCC). This combination therapy approach may provide enhanced treatment options for patients with ESCC.
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
