Please complete the online exercise. OPTIONAL‐Please participate in the online discussion forum.
Ligand lipophilicity efficiency Background: Molecular indexes and metrics allow members of a drug discovery team to quickly prioritize one hit above another. Instructions: Read the passage below on another metric, ligand lipophilicity efficiency, by which hits may be prioritized. Use the information on ligand lipophilicity efficiency to answer the questions that follow. Learning Goal: To learn another molecular index by which the quality of a hit can be gauged. A frequently encountered molecular index is ligand lipophilicity efficiency, or LLE.1 (Do not confuse LLE with LE, the visually similar but very different ligand efficiency.) LLE is the difference between a drug's activity in the form of −log IC50 or −log Ki and a drug's lipophilicity in the form of log P. A more highly positive value for LLE is more favorable. LLE acknowledges the reality that additional activity (a larger value for −log IC50.) is obtained by adding molecular weight and likely increasing lipophilicity (a larger value for log P). According to Lipinski's rule, log P has a maximum value of 5. Therefore, hits with a value for log P closer to 5 and only hit‐like activity have low values for LLE leave little room in terms of lipophilicity for growth of the molecule. LLE creates a direct relationship between activity and lipophilicity. A more active molecule will have a larger, positive value for −log IC50. 1. Edwards, M. P.; Price, D. A. Role of Physiochemical Properties and Ligand Lipophilicity Efficiency in Addressing Drug Safety Risks. Annu. Rep. Med. Chem. 2010, 45, 2615‐2623. Please complete the online exercise. OPTIONAL‐Please participate in the online discussion forum.
10.5 Filtering Hits Pt 3 Other lead selection criteria video Please watch the online video (7 minutes 59 seconds). A condensed summary of this video can be found in the Video summary page.