Many of our clients, particularly in the DMPK field of research, are familiar with the HUREL® micro liver platform – a leader in the realm of physiologically relevant hepatocyte systems. Acquired in 2021, the HUREL® micro liver model was integrated into Visikol’s portfolio as a ready-to-use 2D cell culture plate that offered robust metabolic competency and long-enduring phenotypic stability due to its near 60% hepatocyte density – similar to an in vivo system. What many clients may not know is that HUREL® is also offered as a service in a variety of research applications, a few of which we will explore below.
Cytotoxicity and Hepatotoxicity Screening: The cytotoxicity and hepatotoxicity screening service makes early, high-acuity assessment of hepatotoxic risk cost-effective for smaller organizations and thereby brings new illumination to the challenge of reducing late-stage candidate attrition. This service is available in all HUREL® models with an ATP readout as its main endpoint, and is ideally applied during the early lead selection stage of preclinical discovery/development.
Multi-Parameter Toxicity (HUREL Tox™): The Multi-Parameter Toxicity assay applies HUREL® ’s superior metabolic competency to a panel of complementary assays, creating a multi-parametric characterization of hepatotoxic risk. HUREL Tox™ incorporates a 14-day, repeat-dose cytotoxicity study with both ATP and albumin (ELISA) readouts. Computation of time-based HUREL ratios™ and ACEA RTCA impedance signal indices illuminate potential chronic liabilities of pre-candidate NME’s. Incubation in the absence and presence of broad CYP inhibitor aminobenzotriazole (ABT) reads on the potential for formation of reactive metabolites. Incubation in the absence and presence of bile salts provides a marker of potential cholestatic liability. Lastly, the HUREL Tox™ assay panel can be custom-configured according to the client’s particular study design.
Metabolic Clearance: The HUREL® micro liver coculture system is a robust and reliable method for human in vivo clearance prediction and metabolite detection of slowly metabolized drugs. The coculture system has similar phase I and phase II enzyme activity as freshly thawed hepatocytes for at least 10 days, which enables a range of in vitro studies to predict the human in vivo situation. The system has been thoroughly validated by many companies such as AstraZeneca, as demonstrated in the following article:
Metabolite Generation and ID: HUREL micro livers produce robust metabolite yields that closely correlate to metabolites generated by parent compounds in vivo. HUREL® ‘s met-gen competency is species-specific—including monkey, rat, and dog.
Reaction Phenotyping Assay: Visikol utilizes the HUREL Human Pool™ Primary Hepatocyte Micro Liver Model, which maintains stable metabolic activities in long-term cultures (> 4 weeks). This model is more physiologically relevant and has a complete complement of drug metabolizing enzymes (CYPs and non-CYPs) and cofactors. Using HUREL Human Pool™ primary hepatocyte micro liver model, intrinsic clearance rates for parent drug depletion in the absence and the presence of CYP inhibitors are measured to determine the contribution of CYP enzymes. This information is useful to identify the specific enzymes responsible for the drug metabolism.
Visikol’s HUREL® micro liver system is a key player in the DMPK space, with its users ranging from large pharmaceutical companies to chemical and pesticide manufacturers. Whether you have a cell culture lab on site or not, Visikol has got you covered! Reach out today to learn more about HUREL® products and services: Request Quote