Case Study: Example of Initial ADMET Screen

Background:

The client had compounds with novel structures for use in the treatment of respiratory disorders. The first batch of analogs had been synthesized and was in the process of going through in vivo testing. Potential ADMET problems to be addressed by the medicinal chemistry program needed to be identified.

Problem:

• Nothing was known about the ADMET properties of the compounds.
• The target was unidentified.
• No in vitro assay for efficacy was available.
• Preliminary in vivo results did not match with predictions of efficacy based on structure.

The cost and duration of in vivo testing required careful pre-selection of compounds. It was necessary to identify the ADMET issues associated with each compound and to come up with a paradigm to apply to the compounds to take forward to the animal study.

Solution:

• Apredica scientists consulted with the client on the chemistry of the compounds and implemented assays to determine drug-drug interactions, stability, solubility, Caco-2 permeability and cytotoxicity of the compounds.
• Apredica identified the major ADMET liability: fast plasma metabolism of the compounds.
• Apredica developed a custom assay to screen compounds prior to in vivo testing and ranked the compounds according to their ADMET liability.

Results:

With the data provided by Apredica, the client was able to prioritize compounds for animal studies.

Contact us to learn more about Apredica's initial ADMET screening services.