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1. The physicochemical properties of small-molecule drugs are concentrated in a narrow range known as "drug-like" space, and certain properties like lipophilicity and hydrogen bond donor count have remained constant in oral drugs over time.

2. Investigational drugs over the past three decades have become more lipophilic, larger, and less three-dimensional than approved oral drugs, which can lead to higher attrition rates at each stage of clinical development.

3. Monitoring and optimizing ligand efficiency metrics instead of potency alone can help remedy the overemphasis on potency and associated tendency to inflate physicochemical properties in drug discovery. Ligand efficiency metrics quantify how effectively a molecule uses its structural features in binding to the target.

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