Using Cell Microarrays to Detect Off-Target Effects in Drug Development

A primary concern in drug development is the binding of drugs to targets they are not supposed to bind to. As a result, off-target effects can occur, which may have severe toxicological consequences in patients. Researchers can use cell microarrays to identify potentially dangerous off-target interactions of new therapeutic molecules to de-risk research programs, increasing patient safety, and improving success rates in regulatory submissions.

Assessing the off-target liability of therapeutic candidates is critical for companies, particularly when filing investigational new drug (IND) data to start in-human clinical trials. To verify that binding of drug candidates occurs in the target tissue only, so-called tissue cross-reactivity (TCR) studies are traditionally conducted.

Drug candidates are incubated with cryosections from a standard panel of human tissues and analyzed by immunohistochemistry (IHC). IHC-based TCR allows therapeutic developers to detect drug-target interactions through enzymatic color changes, which are visualized microscopically. 

Nick Brown, Charles River Laboratories, Retrogenix, cell microarraysNick Brown, leader of the UK-based High Peak Client Service Team, Charles River Laboratories

IHC-based TCR approaches are excellent tools to determine the ‘where’ – the location of molecular interactions within a histological context,

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