What question did this study set out to answer?

The study aims to discover novel KRAS inhibitors using computational methods, targeting pancreatic and colorectal cancers.

April 1, 2026

Discovery of novel KRAS inhibitors: A computational study

Puntos clave

The study aims to discover novel KRAS inhibitors using computational methods, targeting pancreatic and colorectal cancers.
Retrieving compounds from the ZINC database based on pharmacophore and 3D-QSAR models.
Using virtual molecular docking studies with PDB ID: 7O83 to evaluate compound interactions.
Conducting ADME studies to assess drug-like characteristics and molecular dynamics simulations for stability analysis.
Three compounds showed competitive docking scores compared to standard drug Sotorasib.
ADME studies indicated favorable drug-like properties for selected compounds.
Molecular dynamics simulations confirmed the stability of ligand-protein complexes throughout the process.

Resumen

KRAS is the most common altered oncogene of the RAS family in human tumors emerging as an attractive target for various human tumors. KRAS is found to be responsible for activating mutations upto 90% in pancreatic cancers and 50% in colorectal cancers. The present study involved retrieving a set of compounds from the ZINC database based on the best pharmacophore hypothesis/model and the optimal 3D-QSAR model (R 2 = 0.943; Q 2 = 0.9423), indicating strong correlation and predictive ability, along with low standard deviation (SD = 0.3987) and RMSE (0.38). In addition, 3D contour maps were examined to identify favorable and unfavorable regions for enhancing drug activity. The selected compounds were further screened through virtual molecular docking studies using PDB ID: 7O83. Three compounds-ZINC1911582104, ZINC1911585886, and ZINC1569989248 demonstrated comparable XP docking scores of -9.281, -8.112, and -7.261, respectively, relative to the standard drug Sotorasib (docking score: -9.232).Also, ADME studies suggested drug-like characteristics of the compounds ZINC1911582104, ZINC1911585886 and ZINC1569989248. Further, molecular dynamics simulation studies supported the stability of the ligand-protein complex during the course of the simulation. As a result, the present research may help scientists in beating the fight against undruggable KRAS target.

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Cite This Study

Wahan et al. (Fri,) studied this question.

synapsesocial.com/papers/69ccb63f16edfba7beb87e4d https://doi.org/https://doi.org/10.1142/s2737416526500729

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