A three-stage experimental strategy to evaluate and validate an interplate IC50 format

Area of Science:

• Biochemistry
• Pharmacology
• Drug Discovery

Background:

• Serial dilution for compound potency determination can be a bottleneck in research projects.
• Traditional methods for establishing 50% inhibitory concentration (IC50) can be time-consuming.

Purpose of the Study:

• To investigate the feasibility of an interplate format for IC50 experiments.
• To develop and validate a strategy for assessing interplate assay data quality compared to intraplate formats.
• To enhance the throughput and efficiency of compound testing in drug discovery.

Main Methods:

• A three-stage approach was adopted to assess and validate the interplate format against the intraplate format.
• Dose ranges were constructed across plates to facilitate interplate IC50 experiments.
• The strategy was tested using two different assay formats.

Main Results:

• The interplate format demonstrated potential for faster reformatting and generation of more doses.
• This approach can lead to higher-throughput and more timely compound testing.
• The feasibility assessment strategy ensured data quality equivalent to historical formats.

Conclusions:

• An interplate format for IC50 determination is feasible and offers advantages in speed and throughput.
• The proposed three-stage strategy is effective for validating new assay formats.
• This methodology can be adapted to assess other assay types for improved drug discovery efficiency.