WuXi AppTec in vitro Safety Pharmacology Profiling

Comprehensive in vitro off-target screening services

Safety-related drug failure is a major challenge for the pharmaceutical industry. Approximately 75% of adverse drug reactions (ADRs) are dose-dependent, related to a pharmacological action of the drug, and predictable. The interactions of drugs with off-target proteins have conventionally been viewed as undesirable ‘promiscuity’, responsible for unwanted side effects.

Secondary pharmacology studies evaluate compound promiscuity against a broad range of targets that are related to or distinct from the intended therapeutic target. This is a cost-effective approach used by many pharmaceutical companies as a safety screen early in the drug discovery process, to predict clinical adverse effects and to reduce safety-related attrition.

WuXi Biology provides in vitro safety pharmacology services to identify potential off-target liabilities. Three choices can be selected:

• WuXi AppTec Mini Safety 44 Panel (Mini Safety 44 Panel)
A primary safety panel, which is designed to identify compounds with the highest risk because it contains targets associated with the most serious adverse drug reactions (ADRs). This panel is recommended for use early in the drug discovery process, for early hazard identification.
The 44 selected targets are recommended by four major pharmaceutical companies (Bowes J. et al. Nat Rev Drug Discov. 2012), including 24 GPCRs, 8 ion channels, 7 enzymes, 3 monoamine transporters and 2 nuclear hormone receptors.

• WuXi AppTec Second Safety 54 Panel (Safety Extra 54 Panel)
A panel of additional 54 targets. This more extensive panel contains such targets that have the combination of either low-hit-rate/high-risk ADRs or high-hit-rate/ lower-risk ADRs. This panel is ideal for broad characterization of a limited number of compounds for lead selection, providing data to drive SAR for lead optimization.
The 54 selected targets include 26 GPCRs, 5 ion channels, 18 enzymes, 3 nuclear hormone receptors and 2 transmembrane targets.

• WuXi AppTec Full Safety 98 Panel (Safety 98 Panel)
The combination of Mini Safety 44 Panel and Safety Extra 54 Panel.