Phenotypic screening

Phenotypic screening is a method used in biological research and drug discovery to identify substances such as small molecules, genetic perturbations or microorganisms that alter the phenotype of a cell or an organism in a desired manner. This method is used to study various diseases and their potential treatments.

Overview

Phenotypic screening involves the use of high-throughput screening technologies to test a large number of potential drug compounds. The goal is to identify those that have a desired effect on a particular phenotype. This approach contrasts with target-based screening, which starts with a known drug target and screens only for compounds that affect this target.

History

Phenotypic screening has a long history in drug discovery. Many of the most important drugs were discovered through phenotypic screening, including penicillin, aspirin, and metformin. However, with the advent of genomics in the 1990s, many pharmaceutical companies shifted their focus to target-based screening. This trend has reversed in recent years, with a renewed interest in phenotypic screening due to its potential to discover more novel and effective drugs.

Methodology

Phenotypic screening typically involves the following steps:

1. Preparation of the test system: This could be a cell line, a primary cell culture, an organism, or a model of a disease.
2. Treatment with test substances: These could be small molecules, genetic perturbations, or microorganisms.
3. Measurement of phenotypic changes: This is usually done using high-throughput screening technologies.
4. Data analysis: The data is analyzed to identify substances that cause a desired change in phenotype.

Advantages and Disadvantages

Phenotypic screening has several advantages over target-based screening. It can discover drugs that work through novel mechanisms of action, and it can identify drugs that have multiple targets, which could be beneficial for treating complex diseases. However, phenotypic screening also has some disadvantages. It can be more difficult and time-consuming to identify the target of a drug discovered through phenotypic screening. In addition, phenotypic screening may not be suitable for all types of diseases.

See Also

• High-throughput screening
• Drug discovery
• Pharmacology
• Genomics