2D QSAR approach to develop newer generation molecules active aganist ERBB2 receptor kinase as potential Anticancer Agent
Supriyo Saha, Amartya Banerjee, Ayan Rudra · Scholar Science Journals - International Journal of Biomedical Research · 2015
Quantative Structure Activity Relationship analysis was performed using 159 molecules active against ERBB2 kinase inhibitory activity, where IC50 was converted into pIC50. The statistically suitable QSAR model was PIC50 = -0.27351(+/-1.85955) -0.02792(+/-0.08389) ALogP -2.14626(+/-1.14052) SpMin3_Bhv -1.32984(+/-0.13918) ntN +0.21209(+/-0.02129) ETA_Beta_ns (SEE :0.63346, r^2 :0.56219, r^2 adjusted :0.54627, F :35.31334 (DF :4, 110) which suggest that electron-richness of the molecule (ETA_Beta_ns) will create positive response and Ghose-Crippen LogKow value (ALogP), Smallest absolute eigenvalue of Burden modified matrix - n 3 / weighted by relative van der Waals volumes (SpMin3_Bhv) and number of atom type E state (ntN) cause negative response in biological activity. Then the model was validated by Golbraikh and Tropsha acceptable criteria as Q^2: 0.51805 Passed (Threshold value Q^2>0.5),r^2 :0.60327 Passed(Threshold value r^2>0.6), |r0^2-r'0^2|:0.18983 Passed (Threshold value |r0^2-r'0^2| 0.3. The External Validation Parameters(Without Scaling): r^2 :0.60327 and external Validation parameters (After Scaling): rm^2 :0.5955. The model was cross validated using Leave-One-Out (LOO) process with Q2:0.51805, PRESS: 48.59098, SDEP :0.65002.So the QSAR model was suitable for future development.