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- Q13611503 subject Q7056690.
- Q13611503 subject Q7300121.
- Q13611503 abstract "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. These lead compounds undergo more extensive optimization in a subsequent step of drug discovery called lead optimization (LO). 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 developmentThe hit to lead stage starts with confirmation and evaluation of the initial screening hits and is followed by synthesis of analogs (hit expansion). Typically the initial screening hits display binding affinities for their biological target in the micromolar (10−6 molar concentration) range. Through limited H2L optimization, the affinities of the hits are often improved by several orders of magnitude to the nanomolar (10−9 M) range. The hits also undergo limited optimization to improve metabolic half life so that the compounds can be tested in animal models of disease and also to improve selectivity against other biological targets binding that may result in undesirable side effects.On average, only one in every 5,000 compounds that enters drug discovery to the stage of pre-clinical development becomes an approved drug.".
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- Q13611503 wikiPageWikiLink Q7056690.
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- Q13611503 wikiPageWikiLink Q7300121.
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- Q13611503 comment "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. These lead compounds undergo more extensive optimization in a subsequent step of drug discovery called lead optimization (LO).".
- Q13611503 label "Hit to lead".