Drug discovery model using molecular orbital computations: tyrosine kinase inhibitors

Clifford Fong (1)

1 Eigenenergy

Abbreviations TKI Tyrosine kinase inhibitors, MKI Multi-kinase inhibitors, CML chronic myeloid leukaemia, organic cation uptake transporter OTP, organic anion uptake transporter OATP, organic cation influx transporter OCT, SDF surface distribution function, RDF the water radial distribution function, ΔG desolvation free energy of water desolvation, ΔG lipophilicity free energy of lipophilicity or hydrophobicity, ΔG desolv,CDS free energy of water desolvation of the cavitation dispersion solvent structure (CDS), ΔG lipo,CDS free energy of lipophilicity or hydrophobicity for the CDS, DM dipole moment DM, SASA solvent accessible surface area, R 2 multiple correlation coefficient, F the F test of significance, SEE standards errors for the estimates, SE(ΔG desolvation) standard errors of ΔG desolvation , SE(ΔG lipophilicity), standard errors of ΔG lipophilicity , SE(Dipole Moment) standard errors for dipole moments, SE (Molecular Volume) standard errors for molecular volumes as calculated from " t " distribution statistics, QM quantum mechanics, DDR Discoidin domain receptor, PDGFR platelet-derived growth factor receptors Abstract It has been shown that equation 1 can be successfully applied to the competitive binding of a number of tyrosine kinase inhibitors and multi-kinase inhibitors to a range of kinase enzymes. Equation 1 also applies to the active competitive transport of these tyrosine kinase inhibitors by the hOCT3, OATP1A2 and OCT1 transporters. There is strong independent evidence from the literature that ΔG desolvation , ΔG lipophilicity , the dipole moment and molecular volume are good inherent indicators of the transport or binding ability of drugs.

Domaines: Chimie théorique et/ou physique; Chimie thérapeutique

Clifford Fong. Drug discovery model using molecular orbital computations: tyrosine kinase inhibitors. 2016. ⟨hal-01350862⟩