TY  - JOUR
A1  - Sarukhanyan, Edita
A1  - Shityakov, Sergey
A1  - Dandekar, Thomas
T1  - Rational drug design of Axl tyrosine kinase type I inhibitors as promising candidates against cancer
JF  - Frontiers in Chemistry
N2  - The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors.
KW  - Axl tyrosine kinase
KW  - anti-cancer drug-like molecules
KW  - rational drug design
KW  - molecular docking
KW  - molecular dynamics
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199505
SN  - 2296-2646
VL  - 7
IS  - 920
ER  -