How and When to Use In Vitro Safety Pharmacology Profiling

SecEHfdaiy in vitro Ptiarmacotcgy Pecapuirs 46% Transponera 4 H Enzymes 44 % lan channala B % 

A smaller (prima ) panel of targets is usually sufficient during the hit to lead phase and lead optimization phases of a drug discovery program to detect promiscuous scaffolds and 

Assess risk of remaining liabifHies with respect to enposure anti indication 

At lead selection, after which typically more chemistry effort is invested, the selected compounds can be profiled in a broader (secondary) panel of assays, hopefully confirming the selective nature of the leads. If this is the case, spot checking in the primary panel through the optimization phase may be sufficient to ensure selectivity is retained while the required potency at the primary target is achieved. If the selected leads are still rather promiscuous, or certain individual unwanted liabilities remain, these should be monitored by testing in the primary panel (or in additional individual assays) and improved upon during lead optimization. Tfie broader panel can then be applied again to the selected development candidates for a final check and these may even be extended further to additional specialized panels for added security. 

At this point in the program, key information from other in vitro and in vivo studies become available, such as efficacy, pharmacokinetics, potential drug-drug interactions, metabolites and some early toxicology. All of these factors combined enable a first integrated risk assessment to be made. 

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