October 2017

Hepatosure Hepatocytes: the largest donor pool for your DMPK applications

Author:  Isabelle Nobiron, tebu-bio
Posted:  18 October 2017

Pooled human hepatocytes can complement a selection of hepatocytes from various species for metabolite profiling, species comparison and evaluation of potential human-specific metabolites. HepatoSure® is the largest pool of human hepatocytes available without the expense of custom pooling, and is designed to facilitate your DMPK applications. HepatoSure® is best suited for both discovery and development of ADME-Tox study assays where generation and comparison of data is required. Let’s take a closer look...

Including 100 individual donors (from mixed gender) with little variation from lot-to-lot and large lot sizes, HepatoSure® enables you to minimize assay setup and validation repeats associated with changing donors and lots. The utility of HepatoSure® has been demonstrated with drugs whose hepatic clearance is mediated by various combinations of CYP, UGT and AO activities. Applications recommended for HepatoSure® include evaluation of hepatic metabolism (both CYP and non-CYP enzymes), transporter-mediated uptake, enzyme or transporter inhibition and metabolite profiling and identification.

What are the main benefits of HepatoSure®?

  • 100 donors (reduced inter-individual variability)
  • High viability and enzyme activity levels
  • Extensively characterized using LC-MS/MS methods
  • High quality, reproducible hepatocytes

HepatoSure® – highly characterised

Each lot of HepatoSure® is characterized for activity of several CYPs and other DME enzymes, including multiple cytochrome P450s, UDP-Glucuronosyltransferases (UGT), Sulfotransferases (SULT) and aldehyde oxidase (AO). Several additional drug metabolizing enzyme activities can be characterized upon request as a custom service. The complement of these hepatic enzymes enables the evaluation of several types of metabolism endpoints. HepatoSure® can be used for short- and long-term metabolic clearance studies in suspension and enzyme phenotyping in the presence or absence of specific chemical inhibitors of CYP and/or non-CYP enzymes.

HepatoSure pool of hepatocytes
HepatoSure pool of hepatocytes – characterisation information (Sekisui Xenotech at tebu-bio)

Transporters: Each lot of HepatoSure® is characterized for several hepatic uptake transporters, including OATP1B1 (estrone-3-sulfate), OATP1B3 (CCK-8), OCT1 (MPP+) and NTCP (taurocholate). HepatoSure® serves as an excellent tool to evaluate whether a drug candidate is a substrate for active hepatic uptake with the oil-spin or medium loss methods and, furthermore, to determine active and passive uptake clearances with the aforementioned experimental approaches. Lysosomal trapping or sequestration can also be evaluated with HepatoSure®. Additionally, Transporter phenotyping can be conducted with methods that employ chemical inhibitors (transporter specific).

Transporter or Enzyme Inhibition: With a full complement of drug metabolizing enzymes and transporters, HepatoSure® is an excellent tool for evaluation of enzyme or transporter inhibition. The large number of donors and large lot sizes minimizes the contribution of a single individual or sub-population (e.g. CYP2D6 PM’s) and enables rapid assay development and validation when new lots are needed.

HepatoSure pool of hepatocytes - major P450 activities for 4 different pools, minimum lot-to-lot variability.
HepatoSure pool of hepatocytes – minimum lot-to-lot variability

HepatoSure® OptiThaw Kit – guaranteed post-thaw viability

Sekisui XenoTech’s HepatoSure® pooled human cryopreserved hepatocytes are shipped with a HepatoSure® OptiThaw Kit. This kit contains optimized, proprietary media to ensure consistent yield and high viability post-thaw. Each kit is sufficient to thaw and isolate up to three 1.5mL vials of HepatoSure®. When using the OptiThaw kit per Sekisui XenoTech’s optimized protocols, HepatoSure® pooled cryopreserved human hepatocyte products are guaranteed to yield a post-thaw viability of 70% or higher.

HepatoSure® – optimal performance, lower cost

HepatoSure® was tested against a comparable product currently on the market and demonstrated similar viability, enzymatic activity and overall performance. Costing less than the competition, HepatoSure® includes 100 donors, provides the necessary media for thawing and isolation (HepatoSure® OptiThaw Kit) and delivers high quality, consistent hepatocytes. HepatoSure® is a pooled human hepatocyte product designed to facilitate DMPK applications with a more consistent hepatocyte product year after year.

HepatoSure® – what you’ll receive

  • 1.5 mL (item ref. HCP100.H15)
  • 5 million cells AMY (Assured Minimum Yield)
  • HepatoSure™ OptiThaw Kit included (item ref. K8500)

Contact us if you wish to receive any additional information on Hepatosure or the other products we can provide for your ADME-Tox studies (single-freeze smaller pools or individual donor hepatocytes, subcellular fractions with high custom possibilitiesand much more.

Originally published in tebu-bio's Being Bioreactive. To purchase Sekisui XenoTech's products in the EU, please visit tebu-bio's website.

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