Tier I: Short-term (Max. 7 days)
Screen for potential DILI drugs quickly with high sensitivity and specificity
Liver toxicity caused by exposure to clinical known DILI compounds is best predicted using a 14-day dosing regimen. However, initial screens using shorter dosing protocols permit higher throughput and faster decision making to further progress compounds along the drug-development chain. 3D InSight™ Liver Microtissues are an ideal model for short-term DILI prediction, enabling you to:
- Achieve faster turnaround and higher throughput than 14 day compound exposure regimen with short-term compound exposure (max. 7 days)
- Ensure high DILI sensitivity and specificity to rule out most toxic drugs by conducting a Tier 1 preliminary screen safety test in a 3D primary human liver model
- Advance promising drugs to the next testing level sooner with greater confidence in de-risking decisions
InSphero compared 38 compounds for short-term (5 day) and long-term (14 day) toxicity. In this study, 17 out of 38 drugs did not show any difference between compound exposures, while 21 out of 38 drugs displayed lower IC50 values when exposed for 14 days. Thus, reducing the exposure period from 14 to 7 days (max.) allows quicker turnaround while retaining acceptable sensitivity for hepatotoxicants.
Time dependent changes in IC50 values in 3D InSight™ Human Liver Microtissues for a subset of compounds tested at day 5-6 and 14 of treatment. Lower IC50 values were obtained with 21 out of 38 drugs for which cell viability was determined at days 5-6 (striped) and 14 days (solid black). DILI severity category (1 severe → 5 No DILI) in brackets. Data are n=1 or geomean of n=2-16