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The RAS gene family is one of the most frequently mutated oncogenes in human cancers. In KRAS, mutations of G12D and G12C are common. Here, 52 iridoids were selected and docked against 8AFB (KRAS G12C receptor) using Sotorasib as the standard. As per the docking interaction data, 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (dock score: −9.9 kcal/mol), 6′-O-trans-para-coumaroyl geniposidic acid (dock score: −9.6 kcal/mol), 6-O-trans-cinnamoyl-secologanoside (dock score: −9.5 kcal/mol), Loganic acid 6′-O-beta-d-glucoside (dock score: −9.5 kcal/mol), 10-O-succinoylgeniposide (dock score: −9.4), Loganic acid (dock score: −9.4 kcal/mol), and Amphicoside (dock score: −9.2 kcal/mol) showed higher dock scores than standard Sotorasib (dock score: −9.1 kcal/mol). These common amino acid residues between iridoids and complexed ligands confirmed that all the iridoids perfectly docked within the receptor's active site. The 100 ns MD simulation data showed that RMSD, RMSF, radius of gyration, and SASA values were within range, with greater numbers of hydrogen bond donors and acceptors. MM/PBSA analysis showed maximum binding energy values of −7309 kJ/mol for 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester. FMO analysis showed that 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester was the most likely chemically reactive molecule. MEP analysis data highlighted the possible electrophilic and nucleophilic attack regions of the best-docked iridoids. Of all the best-docked iridoids, Loganic acid passed Lipinski, Pfizer, and GSK filters with a similar toxicity profile to Sotorasib. Thus, if we consider these iridoids to be KRAS G12C inhibitors, they will be a boon to mankind. [ABSTRACT FROM AUTHOR]

[Display omitted] Vascular Endothelial Growth Factor (VEGF) has a greater impact on carcinogenesis, and it is the most significant receptor in mediating the mutagenesis and permeability of endothelial cells. Here, we report the identification of potential VEGFR-2 inhibitors as new putative anti-cancer agents. In this regard, a pharmacophore model was generated, considering established potent VEGFR2 inhibitors. This model was further applied for the virtual screening of the ZINC database and the feature-based design of another eight molecules (B1–B8). Examining these molecules using sequential computational approaches including molecular docking, molecular dynamic simulation, and DFT analysis leads to the identification of compounds B3, B5, and B7 as potential inhibitors that showed better binding affinity, stability, and interaction mechanisms concerning the reference control, Sorafenib. Further, the Lipinski rule filters and ADMET analysis support the selected compounds as drug candidates subjected to experimental validation. [ABSTRACT FROM AUTHOR]