Which parameter sets are applied to hits during drug discovery screening?

Which parameter sets are applied to hits during drug discovery screening?

• A. Lipinski's Rule of 5 Only
• B. Veber's Parameters Only
• C. Hansch Substituent Constants
• D. Lipinski's Rule of 5 and Veber's Parameters

Answer: (D)

In drug discovery, early hit filtering uses drug-likeness criteria to predict whether a compound is likely to be orally bioavailable. Lipinski's Rule of Five gives quick thresholds: molecular weight under about 500 Da, logP not greater than 5, no more than 5 hydrogen-bond donors, and no more than 10 hydrogen-bond acceptors. Veber's parameters refine this further by emphasizing molecular rigidity and polar surface area: ideally no more than 10 rotatable bonds and a polar surface area (PSA) of around 140 Ų or less. Using both sets together helps flag hits that are more likely to be permeable, soluble, and orally bioavailable, guiding prioritization toward compounds with better developability. Hansch substituent constants are used in SAR/QSAR to relate substituent effects to properties like lipophilicity and activity, but they aren’t standard screening filters for hits.

In drug discovery, early hit filtering uses drug-likeness criteria to predict whether a compound is likely to be orally bioavailable. Lipinski's Rule of Five gives quick thresholds: molecular weight under about 500 Da, logP not greater than 5, no more than 5 hydrogen-bond donors, and no more than 10 hydrogen-bond acceptors. Veber's parameters refine this further by emphasizing molecular rigidity and polar surface area: ideally no more than 10 rotatable bonds and a polar surface area (PSA) of around 140 Ų or less. Using both sets together helps flag hits that are more likely to be permeable, soluble, and orally bioavailable, guiding prioritization toward compounds with better developability. Hansch substituent constants are used in SAR/QSAR to relate substituent effects to properties like lipophilicity and activity, but they aren’t standard screening filters for hits.