Can BDDCS illuminate targets in drug design?

Area of Science:

• Pharmacology
• Drug Discovery
• Biochemistry

Background:

• Pharmacokinetic (PK) properties of drugs are known to influence target interactions.
• The reciprocal relationship, where targets influence drug PK properties, remains largely unexplored.

Purpose of the Study:

• To investigate the influence of target protein families on the pharmacokinetic (PK) properties of drugs.
• To establish a novel paradigm for drug discovery by integrating PK considerations at the target selection stage.

Main Methods:

• Cross-referencing 'druggable target' annotations for over 1000 FDA-approved drugs.
• Analyzing drug PK profiles using the Biopharmaceutics Drug Disposition Classification System (BDDCS).
• Examining BDDCS preferences across major target protein families and therapeutic categories.

Main Results:

• Demonstrated that specific protein families exhibit a clear preference for drugs with distinct PK properties.
• Identified significant correlations between target families and drug PK profiles.
• Provided the first evidence for targets influencing drug PK characteristics.

Conclusions:

• Drug targets possess inherent preferences for specific drug pharmacokinetic (PK) profiles.
• This finding offers a novel approach to drug discovery, emphasizing PK considerations during early target selection.
• Recommends integrating PK profiling into the initial stages of identifying and selecting drug targets.