spacer
home > news > detailed info
INDUSTRY NEWS AND PRESS RELEASES

BioIVT Publishes New Research On the Mechanisms Underlying the C-DILI Assay

BioIVT

The C-DILI™ Assay is a highly effective tool for assessing cholestatic hepatotoxicity risk of promising new drug candidates

BioIVT, a leading provider of research models and services for drug development, today announced its research into the mechanisms involved in cholestatic drug-induced liver injury (DILI) has been published in Applied In Vitro Toxicology.1

DILI is one of the primary causes of drug development failures. As a result, sponsors endeavor to identify new drug candidates with a high DILI risk early in the development process. Early cholestatic DILI screening efforts historically focused on a compound’s potential to inhibit BSEP, a protein responsible for excretion of bile acids from the liver. However, BSEP inhibition potency is not always correlated with DILI suggesting that other mechanisms may be involved. BioIVT researchers demonstrated that BSEP inhibition ‘‘triggers’’ the activation of compensatory mechanisms that suppress bile acid synthesis and increase bile acid excretion through routes other than BSEP, thereby preventing hepatotoxicity.

“Cholestatic DILI is known to have a weak association with BSEP inhibition,” said BioIVT Study Director and Lead Author Jonathan Jackson, PhD. “For the first time, our study demonstrated the ‘link’ between BSEP inhibition and FXR, a master regulator of bile acid homeostasis. FXR activation by BSEP inhibition may explain the weak concordance between BSEP inhibition potency and cholestatic DILI incidence. Many compounds inhibit BSEP; however, liver cells can compensate for the resulting increase in bile acid concentration. In fact, clinical observations show that increases in circulating bile acids are not always associated with DILI. Our discovery suggests a new paradigm is required to accurately predict a drug candidate’s cholestatic DILI potential, and new methods are needed, such as our C-DILI Assay.”

The C-DILI Assay integrates cellular compensatory mechanisms with BSEP inhibition. Because the assay accounts for the adaptive response observed in liver cells, it has been shown to have high in vitro-in vivo correlation among compounds known to have a risk of DILI. As part of their screening and drug development processes, pharmaceutical companies use the C-DILI Assay to assess hepatotoxicity potential of their lead compounds.

Reference
1. Jonathan P. Jackson, Kimberly M. Freeman, Robert L. St. ClaireIII, Chris B. Black, and Kenneth R. Brouwer. Applied In Vitro Toxicology. http://doi.org/10.1089/aivt.2018.0011.

About BioIVT

BioIVT, formerly BioreclamationIVT, is a leading global provider of research models and value-added research services for drug discovery and development. We specialize in control and disease-state biospecimens including human and animal tissues, cell products, blood and other biofluids. Our unmatched portfolio of clinical specimens directly supports precision medicine research and the effort to improve patient outcomes by coupling comprehensive clinical data with donor samples. Our PHASEZERO® Research Services team works collaboratively with clients to provide target and biomarker validation, phenotypic assays to characterize novel therapeutics, clinical assay development and in vitro hepatic modeling solutions. And as the premier supplier of ADME-toxicology model systems, including hepatocytes and subcellular fractions, BioIVT enables scientists to better understand the pharmacokinetics and drug metabolism of newly-discovered compounds and their effects on disease processes. By combining our technical expertise, exceptional customer service, and unparalleled access to biological specimens, BioIVT serves the research community as a trusted partner in elevating science. For more information, please visit www.bioivt.com or follow the company on Twitter @BioIVT.
phone +1 516 483 1196
email customerservice@bioivt.com
web www.bioivt.com/
email PO Box 770, Hicksville, NY, 11802-0770
 
Print this page
Send to a friend
   
spacer
News and Press Releases

MedPharm’s CSO and University of Reading Professor co-author new book on dermal formulation development

MedPharm’s Chief Scientific Officer and Co-Founder, Professor Marc Brown and University of Reading’s Professor Adrian Williams have co-authored the new book: ‘The Art and Science of Dermal Formulation Development”. It is the latest addition to ‘Drugs and the Pharmaceutical Sciences’, a series of textbooks and monographs published by CRC Press.
More info >>


White Papers

Faster, Better, Cheaper: Lean as a Driving Force Behind Pharmaceutical Companies’ Growth

TBM Consulting Group

The pharmaceutical industry faces countless challenges: patent expirations, weak product development pipelines, downward pricing pressure and an increasingly burdensome regulatory environment. The most important question for companies is now “How can we position ourselves optimally to be successful in the long term?” Some pharmaceutical companies used the economic downturn in 2009 to embrace measures in the fields of cost reduction and efficiency increases, which can be implemented at short notice. The continuous and consistent implementation of sustainable measures that guarantee stability and form the basis for future growth was not necessarily paramount within this.
More info >>

Industry Events

The Universe of Pre-filled Syringes and Injection Devices

22-23 October 2019, The Swedish Exhibition & Congress Centre Gothia Towers Hotel

PDA’s Universe of Pre-filled Syringes and Injection Devices has become the must-attend meeting for everyone working in the field, and is now the world’s largest conference on this subject
More info >>

 
©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement