Defination lead compound in drug discovery and devlopment
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The drug discovery process involves the use of high-throughput screening (HTS) techniques to screen 1000s of compounds and to identify potential drug candidates for a given target (protein, receptor, etc). The compounds which show good activity in the HTS assay are called 'Actives'. These are impure compounds that show good (preset value) activity, judged based on IC50 or EC50 values for that particular target.
Structural similar 'actives' are clustered into groups called 'clusters' and re-screened. From the top 'cluster', most active compounds are re-synthesized with higher purity and re-screened for potency and physical properties (checked for compliance with Lipinski's rule of five). The best (100-200) compounds from these screens are selected for further screening and are called 'Hits'.
From these 'hits' 2-3 compounds are selected based on good structure-activity relationship (SAR) and ADME profile for further optimization. These are known as the lead compounds. These compounds are used as templates for designing other compounds through minor chemical modifications and screened using ex-vivo and in-vivo assays. The compounds with the best pharmacological and pharmacokinetic profiles are selected as 'Drug candidates'
Structural similar 'actives' are clustered into groups called 'clusters' and re-screened. From the top 'cluster', most active compounds are re-synthesized with higher purity and re-screened for potency and physical properties (checked for compliance with Lipinski's rule of five). The best (100-200) compounds from these screens are selected for further screening and are called 'Hits'.
From these 'hits' 2-3 compounds are selected based on good structure-activity relationship (SAR) and ADME profile for further optimization. These are known as the lead compounds. These compounds are used as templates for designing other compounds through minor chemical modifications and screened using ex-vivo and in-vivo assays. The compounds with the best pharmacological and pharmacokinetic profiles are selected as 'Drug candidates'
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