Hit to lead (H2L) also known as lead generation is a stage in early drug discovery where small molecule hits from a high throughput screen (HTS) are evaluated and undergo limited optimization to identify promising lead compounds.[1][2] These lead compounds undergo more extensive optimization in a subsequent step of drug discovery called lead optimization (LO).[3][4] The drug discovery process generally follows the following path that includes a hit to lead stage:
- target validation (TV) → assay development → high-throughput screening → hit to lead (H2L) → lead optimization (LO) → preclinical drug development → clinical drug development
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