R428 | Potent and selective AXL inhibitor

R428 (1037624-75-1) is a potent and selective inhibitor of AXL kinase (IC₅₀ = 1.4nM).¹ R428 has been shown to overcome chemotherapy resistance to various agents in multiple cancer models.^2-5 AXL has been shown to suppress myeloid cell activation and function – combined AXL inhibition with R428 and PD-1 blockade showed potent synergistic antitumor effects.^6,7

References/Citations:

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

Suppression and Enhances Chemotherapy in Pancreatic Cancer; Cancer Res. 78 246