# Computer-Aided Drug Design Boosts RAS Inhibitor Discovery
## 3 Application of CADD Methods in the Development of RAS Inhibitors
### Other CADD Applications
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Targeting** & **Drug** & **Targeting Information** & \multicolumn{5}{c}{**CADD Methods**} & **Reference** \\ \cline{5-6}
**Strategy** & **Drug** & **Targeting Information** & \multicolumn{1}{c}{**Virtual**} & **Screening** & **Ligand-Based** & **Receptor-Based** & **Reference** \\ \hline \hline \multirow{8}{*}{Indirect targeting KRAS} & \multirow{4}{*}{NHTD} & disrupting KRAS-PDES & \multirow{4}{*}{**Legend-based**} & \multirow{4}{*}{**Receptor-Based**} \\  & & interaction, redistributing the localization of KRAS to & & & & [80] \\  & & endmembers by targeting the & & & & \\  & & prepyl-binding pocket of PDES & & & & \\ \cline{2-6}  & \multirow{4}{*}{Antroquinned} & Inhibiting preyltransferase & \multirow{4}{*}{**Cry**} & \multirow{4}{*}{Molecular docking} & \multirow{4}{*}{[93]} \\  & & RAS-related GTP-binding & & & & \\  & & protein activation & & & \\ \cline{2-6}  & \multirow{4}{*}{Theaflavin} & Targeting famesyltransferase, & & Molecular docking: & \\  & & inhibiting PTM process & & Molecular & [78] \\ \hline \multirow{4}{*}{Upstream signaling pathway} & \multirow{4}{*}{Daidzein} & Interacting with the kinase & \multirow{4}{*}{**Cry**} & Molecular docking: & \multirow{4}{*}{[133]} \\  & & domain of the EGFR protein & & & Molecular & \\  & & & domain of the EGFR protein & & & \\  & & & & & \\ \cline{2-6}  & \multirow{4}{*}{Scopoletin} & In targeting EGFR, BRAF and & & & Molecular docking & [134] \\  & & ART1 in NSCLC & & & & \\ \hline \multirow{8}{*}{Purine-2,6-dione analogues} & \multirow{4}{*}{Inhibiting BRAF protein kinase} & \multirow{4}{*}{**Molecular docking**} & \multirow{4}{*}{[94]} \\  & & Inhibiting V600E BRAF & & & & \\  & & RAS-RAF-MEK-ERK signaling pathway) & & & & \\ \cline{2-6}  & phosphoaminophenophonic acid adenylate ester (ANP), phospho-aminophenophonic acid guanylate ester (GNP) & & Stabilizing RASSF2 (a & & \\  & & KRAS-specific effector protein, promoting apoptosis and cell cycle arrest) & & & & \\ \cline{2-6}  & newly designed & \multirow{4}{*}{Inhibiting V600E BRAF} & \multirow{4}{*}{QSAR} & Molecular docking (for the consideration of the similarity and alignment) & & \\ \cline{2-6}  & & Interacting with the RAF kinase & \multirow{4}{*}{Dehydrocoelentrazine ligand-binding pocket, thus inhibiting RKIP} & & Pharmacophore Modelling & Molecular docking & [130] \\ \cline{2-6}  & & in-binding RKIP & & Modelling & & \\ \cline{2-6}  & \multirow{4}{*}{NCI 94680 NCI spafflaw} & \multirow{4}{*}{BRAF inhibitor} & \multirow{4}{*}{**Cry**} & QSAR; & \multirow{4}{*}{Molecular docking} & \multirow{4}{*}{[131]} \\  & & & & & & \\ \cline{2-6}  & \multirow{4}{*}{PICK-\(\alpha\) inhibitor} & \multirow{4}{*}{**Cry**} & QSAR; & \multirow{4}{*}{Molecular docking} & \multirow{4}{*}{[59]} \\  & & & & & & \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & \multirow{4}{*}{PICK-\(\alpha\) inhibitor} & \multirow{4}{*}{**Cry**} & Pharmacophore Modelling & Molecular docking & [59] \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & \multirow{4}{*}{MEK1 inhibitor} & \multirow{4}{*}{**Cry**} & Similarity searching & Molecular docking & [83] \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & \multirow{4}{*}{Catchin} & \multirow{4}{*}{MEK1 inhibitor} & \multirow{4}{*}{**Cry**} & Similarity searching & Molecular docking & [136] \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & & & & & & \\ \cline{2-6}  & & & & & & \\ \hline CID-20/59629 &
\begin{tabular}{c} PI3 Ky/AKT/mTOR \\ pan-inhibitor \\ \end{tabular} & \multirow{4}{*}{\(\checkmark\)} & Similarity searching & Molecular docking & [135] \\ \cline{2-6}  & & & & & & \\ \hline Compound **17** & mTOR inhibitor & \(\checkmark\) & Similarity searching & Molecular docking & [136] \\ \hline \hline \end{tabular}
\end{table} 
Table 5: _Cont._ABACUS by [PERSON] et al. [138].