In silico screening of FDA approved drugs on AXL kinase and validation for breast cancer cell line

Abstract

AXL kinase has been over expressed in many tumors and its involvement in cell proliferation, migration, survival, and resistance makes the kinase as attractive therapeutic target for many cancers. In this study, we performed a virtual screening of the food and drug administration (FDA) approved drug molecule database against AXL kinase for repurposing studies of breast cancer. We have identified three non-cancer drugs with good binding energies were subjected to in vitro breast cancer MCF-7 cell lines. Three drug molecules showing the activity with good IC50 values toward the cancer cell line. We also carried out a 2 dimensional (2 D) quantitative structure activity relation (QSAR) studies on N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides derivatives to design potent inhibitors for AXL kinase. The final QSAR equation was robust with good predictivity and the statistical validation having R² and Q² values are 0.91 and 0.86, respectively. QSAR equation descriptors informs about the chemical properties of AXL inhibitors and helpful for designing novel inhibitors.

Communicated by Ramaswamy H. Sarma

Keywords:

• AXL kinase
• virtual screening
• QSAR
• MCF-7
• molecular dynamics simulations
• drug repurposing

Disclosure statement

No potential conflict of interest was reported by the author(s).