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High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
The search for orally active medications through combinatorial chemistry
R A Fecik1, K E Frank, E J Gentry
1Department of Medicinal Chemistry, Kansas University, Lawrence 66045-2506, USA.
Medicinal Research Reviews
|May 14, 1998
Summary
This review examines combinatorial chemistry libraries for drug-like molecules, focusing on ADME properties. It assesses existing libraries for their potential to yield compounds with good oral bioavailability.
Area of Science:
- Medicinal Chemistry
- Drug Discovery
- Pharmacokinetics
Background:
- Combinatorial chemistry enables rapid synthesis of large molecule libraries.
- Drug-like properties, including ADME, are critical for successful drug development.
- Oral bioavailability is a key factor for convenient drug administration.
Purpose of the Study:
- To review literature on combinatorial chemistry concerning ADME properties.
- To evaluate existing drug-like molecule libraries for oral bioavailability potential.
- To highlight considerations for designing future libraries with improved pharmacokinetic profiles.
Main Methods:
- Literature review of combinatorial chemistry.
- Analysis of published libraries for drug-like properties.
- Assessment of ADME (Absorption, Distribution, Metabolism, Excretion) considerations.
- Evaluation of oral bioavailability likelihood based on molecular properties.
Main Results:
- Many current combinatorial libraries lack sufficient focus on ADME properties.
- A significant portion of evaluated libraries may not yield compounds with optimal oral bioavailability.
- Specific design strategies can enhance the pharmacokinetic profiles of library compounds.
Conclusions:
- Integrating ADME considerations early in library design is crucial for efficient drug discovery.
- Future combinatorial chemistry efforts should prioritize molecules with favorable absorption, distribution, metabolism, and excretion profiles.
- Optimizing for oral bioavailability in library design can accelerate the development of orally administered drugs.
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