On-rate based optimization of structure–kinetic relationship – surfing the kinetic map

• Published in: Drug discovery today. Technologies Vol. 17; pp. 9 - 15
• Main Authors: Schoop, Andreas, Dey, Fabian
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2015
• Subjects: Drug Discovery; Kinetics; Pharmaceutical Preparations - chemistry; Pharmaceutical Preparations - metabolism; Protein Binding; Proteins - metabolism; Structure-Activity Relationship

•We suggest using on-rates as monitoring parameter for SKR.•The overall range for kon optimization is estimated to cover 102–108m−1s−1.•For single targets the variability of kon within a compound series can be limited.•Long residence times can be achieved by affinity optimization despite fast on-rat...