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Updated: Sep 14, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Virtual screening, pharmacokinetic, and DFT studies of anticancer compounds as potential inhibitors
Abdullahi B Umar1, Adamu Uzairu1
1Department of Chemistry, Faculty of Physical Sciences, Ahmad Bello University, Zaria, Nigeria.
Objectives:
V600E-BRAF kinase is an essential therapeutic target in melanoma and other types of tumors. Because of its resistance to known inhibitors and the adverse effects of some identified inhibitors, investigation of new potent inhibitors is necessary.
Methods:
In the present work, in silico strategies such as molecular docking simulation, pharmacokinetic evaluation, and density functional theory (DFT) computations were used to identify potential V600E-BRAF inhibitors from a set of 72 anticancer compounds in the PubChem database.
Results:
Five top-ranked molecules (12, 15, 30, 31, and 35) with excellent docking scores (MolDock score ≥90 kcal mol-1, Rerank score ≥60 kcal mol-1) were selected. Several potential binding interactions were discovered between the molecules and V600E-BRAF. The formation of H-bonds and hydrophobic interactions with essential residues of V600E-BRAF suggested the high stability of these complexes. The selected compounds had excellent pharmacological properties according to the drug likeness rules (bioavailability) and pharmacokinetic properties. Similarly, the energy for the frontier molecular orbitals, such as the HOMO, LUMO, energy gap, and other reactivity parameters, was computed with DFT. The frontier molecular orbital surfaces and electrostatic potentials were investigated to demonstrate the charge-density distributions potentially associated with anticancer activity.
Conclusion:
The identified compounds were found to be potent hit compounds for V600E-BRAF inhibition with superior pharmacokinetic properties; therefore, they may be promising cancer drug candidates.
Insights
New computational methods identified five potent V600E-BRAF inhibitors. These compounds show promise as novel cancer drug candidates due to their strong binding and favorable pharmacokinetic properties.
Area of Science:
- Computational Chemistry
- Medicinal Chemistry
- Oncology
Background:
- V600E-BRAF kinase is a critical therapeutic target in melanoma and other cancers.
- Existing V600E-BRAF inhibitors face challenges with resistance and adverse effects, necessitating new drug discovery.
Purpose of the Study:
- To identify novel, potent V600E-BRAF inhibitors using in silico strategies.
- To evaluate potential drug candidates for anticancer activity against V600E-BRAF.
Main Methods:
- Employed molecular docking simulations, pharmacokinetic evaluations, and Density Functional Theory (DFT) computations.
- Screened 72 anticancer compounds from the PubChem database against V600E-BRAF.
Main Results:
- Selected five top-ranked molecules (12, 15, 30, 31, 35) with high docking scores (MolDock ≥90 kcal/mol, Rerank ≥60 kcal/mol).
- Identified favorable binding interactions (H-bonds, hydrophobic interactions) with V600E-BRAF residues, indicating complex stability.
- DFT analysis revealed favorable electronic properties and charge distributions for anticancer activity.
Conclusions:
- The identified compounds are potent V600E-BRAF inhibitors with excellent drug-likeness and pharmacokinetic profiles.
- These compounds represent promising candidates for developing new cancer therapeutics.
