Mitigating Drug-Induced Liver Injury—Assessing Transporter Liabilities and Bioactivation Transcriptomics, Part 2

ACS Webinars
A drawing of a liver in a torso with the #2 overlaied.

Derisking of drug-induced liver injury (DILI) continues to be a challenge for pharmaceutical scientists.

Join Michael Hafey, Principal Scientist at Merck, as he discusses how to utilize a two-tiered in vitro assay approach to derisk compounds that inhibit bile-salt transport protein, a known mechanism for DILI. Round off your experience listening to Wen Kang, Director of Assay Development and James Monroe, Senior Principal Scientist, both scientists at Merck, as they discuss two seminal 2020 papers where transcriptomics approach in a micropatterned hepatic coculture system or from livers harvested from rats is used to derisk candidates for bioactivation-mediated DILI risk. You will discover the correlation of DILI risk with BSEP inhibition and metabolic activation, along with case examples of how Merck scientists are using cutting edge science to create safe drug molecules.

What You Will Learn

  • The role of key hepatic transporters in drug-induced liver injury and strategies to derisk molecules with transporter-inhibition liability
  • Development of a bioactivation gene signature-based model in detecting hepatotoxicants and its in vivo application in real time to make safe drugs
  • Establishment of an in vitro transcriptomic signature of bioactivation using a micropatterned coculture system (HEPATOPAC®) to derisk compounds early in discovery



Michael Hafey

Jim Monroe

Wen Kang

Kaushik Mitra
Janssen Research & Development

Related Content