Screening of Compounds

We use simple in vitro cell-based assays that can be used for:

  1. Initial screening of compounds for ‘go/no-go’ based decision making
  2. Ranking the compounds based on their cytotoxicity or another endpoint of interest
  3. Initial range finding for determining concentrations of compounds to be used for more complex experiments (e.g., acute studies, transcriptomic assays, mechanism-based specific end point assays)

An example of a simple assay for screening is a version of the HepG2 cytotoxicity and viability assay on the specific compounds that a client is evaluating. We can screen tens or hundreds of compounds at one time with a dose-response reported for each of the compounds. As appropriate, this system can be adapted to include any number of known positive and negative controls or other reference standards.

Using this test protocol, we can measure toxicity at 4, 24, 48, 72 hours after compound administration.  Endpoint of main interest to client is considered. Other factors for consideration include compound potency or equivalent human exposure under normal use.

The inclusion of a relevant simple assay in the workflow will lead to the identification of lead compounds that are less likely to fail compared to using QSAR alone. Depending on the amount of data collected (number of endpoints and frequency of the measurements), the cost can be kept relatively small per batch of up to 30 compounds. Given the cost of conducting this test, we can eliminate from consideration compounds with less desirable results.

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