Zeitschrift für Angewandte Bioinformatik und Computational Biology

In Silico Inhibition Studies of AXL Kinase by Curcumin and its Natural Derivatives

Ghrifi Fatima, Allam Loubna, Lakhlili Wiame and Ibrahimi Azeddine

The last few years have seen the intensive investigation efforts for understanding the wide relevance of AXL activation in multiple aspects of oncogenesis, invasion, metastasis and drug resistance. Therfore, targeting AXL can be considered as one of the promissing approaches for the treatement of cancer. A series of curcumin derivatives which are natural polyphenolic coumponds were wellreported as an anti cancer and chemopreventive agents. We have investigated them as an ATP-competitive inhibitors of AXL kinase by using a docking studies. We built a model of AXL catalytic domain from the crystal structure of proto-oncogene tyrosine-protein kinase MER (MERTK) and the modeling of the three-dimensional (3D) structure of the AXL was performed by SWISS-MODEL homology modeling program. The quality and validation of the model were performed using PROCHECK and VERIFY 3D softwares. The Ramachandran plot was used to validate the overall stereochemical property of the protein. All curcuminoids formed a hydrogen bond with hinge region by Methionine (Met 623) and lysine (Lys 567) indicating that these compounds can be utilized therapeutically as a natural AXL inhibitors.