What are the two basic strategies used to identify hits in drug discovery?

• A. Traditional compound-centered approach and target-centered approach
• B. Random screening and targeted design
• C. In vivo screening and in vitro screening
• D. Structure-based drug design and phenotypic screening

Answer: (A)

The two broad ways to identify hits in drug discovery are compound-centered screening and target-centered screening. In the compound-centered approach, you start with a large, diverse library of compounds and test them in a biological assay to find those that produce the desired effect, without knowing which molecular target is responsible. Once a hit is found, the responsible target can be investigated later. In the target-centered approach, you begin with a defined molecular target and screen for compounds that interact with or modulate that target, leveraging knowledge of the target to guide hit identification and optimization. These two strategies form the foundational split in hit discovery, one focusing on observed biological outcomes and the other on a specific molecular target.