The Microphysiology Systems Database for Analyzing and Modeling Compound Interactions with Human and Animal Organ...

Area of Science:

• Pharmacology
• Toxicology
• Biotechnology

Background:

• Microfluidic human organ models, or microphysiology systems (MPS), are emerging as predictive tools for human drug safety and efficacy.
• Validating MPS requires integrating in vitro data with comprehensive human safety data for reference compounds.

Purpose of the Study:

• To introduce the Microphysiology Systems database (MPS-Db) as a platform for experimental design, data management, and analysis.
• To demonstrate MPS-Db's utility in early drug safety testing by correlating in vitro liver MPS data with in vivo human effects.

Main Methods:

• Development of the MPS database (MPS-Db) for integrating experimental and reference data.
• Utilizing a human liver MPS to evaluate tolcapone and entacapone, known for differing hepatotoxicity profiles despite similar targets and structures.

Main Results:

• The study successfully demonstrated the MPS-Db's capability to link in vitro findings from a human liver MPS to known human in vivo drug effects.
• Tolcapone and entacapone, chosen for their distinct safety profiles, were used to validate the database's predictive power.

Conclusions:

• The MPS-Db is an essential resource for connecting in vitro microphysiology system data with diverse in vivo biochemical, preclinical, and clinical data.
• This database facilitates computational modeling and enhances the predictive accuracy of MPS for human drug safety liabilities.