Skip to main content
Premium Trial:

Request an Annual Quote

Pfizer Uses HCA for Hepatotox Assay, Seeks to Expand Tox Prediction Toolbox

Premium
SAN FRANCISCO — Pfizer researchers have used high-content imaging to develop a cellular hepatotoxicity screen that it will use for certain in vitro drug-development studies.
 
Pfizer’s existing toxicology portfolio comprises micronucleus assays and phospholipidosis assays. Now it plans to add to this mix hepatotoxicity assays, which will enable the company to focus narrowly on the way a single organ responds to drug candidates.
 
The development of the assay is particularly noteworthy for Pfizer after severe cases of hepatotoxicity linked to two of its drugs in recent years compelled the US Food and Drug Administration to issue a public health advisory for one and withdraw the other.
 
The first drug was the antibiotic Trovan. In 1999, one year after it approved the drug, the agency issued a letter to physicians cautioning that six patients died using the drug, and three patients needed liver transplants during a one-year period.
 
The second drug was the diabetes treatment Rezulin. The drug was approved in the US in 1997 and pulled from the market in 2000 after an FDA advisory committee concluded that it poses a greater risk of severe liver toxicity than other drugs in its class.
 
Speaking during the High-Content Analysis 2008 conference, held here this week, Arthur “Russ” Smith, a discovery toxicologist and scientist for Pfizer Global Research and Development, said that the screen is based on approximately 700 compounds.
 
He said the number of compounds will enable the drug maker “to maximize sensitivity to capture hepatotoxicity without generating false positives.”
 
Commenting on the robustness of the assay, Smith said that some drugs found to be hepatotoxic in the initial screen were also observed to be hepatotoxic in animal testing. He declined to elaborate.
 
He said the next step for Pfizer is “to look at the classes of drugs we missed and to build new assays as part of a toolbox of secondary screens that address specific mechanisms relevant to toxicity, such as the inflammatory state in the body,” said Smith.

The Scan

Transcriptomic, Epigenetic Study Appears to Explain Anti-Viral Effects of TB Vaccine

Researchers report in Science Advances on an interferon signature and long-term shifts in monocyte cell DNA methylation in Bacille Calmette-Guérin-vaccinated infant samples.

DNA Storage Method Taps Into Gene Editing Technology

With a dual-plasmid system informed by gene editing, researchers re-wrote DNA sequences in E. coli to store Charles Dickens prose over hundreds of generations, as they recount in Science Advances.

Researchers Model Microbiome Dynamics in Effort to Understand Chronic Human Conditions

Investigators demonstrate in PLOS Computational Biology a computational method for following microbiome dynamics in the absence of longitudinally collected samples.

New Study Highlights Role of Genetics in ADHD

Researchers report in Nature Genetics on differences in genetic architecture between ADHD affecting children versus ADHD that persists into adulthood or is diagnosed in adults.