Understanding P-gp & BCRP Inhibition Assay Design & Outcomes

Aired:  11 December 2018

Presenter: Andrea Wolff, Sekisui XenoTech Director of Services Logistics

In vitro drug transporter inhibition studies are recognized for their importance due to the major role transporters play in absorption, distribution and excretion of compounds, and the toxicological and pharmacological consequences of transporter-mediated drug-drug interactions (DDI). P-gp and BCRP transporters limit intestinal absorption and blood-brain barrier penetration, and facilitate excretion into bile and urine.

Andrea Wolff, Sekisui XenoTech Director of Services Logistics, recently provided a webinar to the SimCyp transporter discussion group on P-gp and BCRP Inhibition. For those who did not have the opportunity to hear her presentation, we hosted a follow-up webinar on Dec. 11th.

Key concepts discussed in this webinar will include:
  • Description of the in vitro test systems used to evaluate P-gp and BCRP inhibition at Sekisui XenoTech and the advantages/disadvantages of these assays
  • Description of the test system qualification process that takes places prior to offering these assays in definitive studies
  • Comparison of IC50 values obtained from the different test systems
  • Comparison of IC50 and Ki values determined with the vesicle test system
  • How IC50 and Ki values are used to evaluate clinical relevance

CryostaX Pellets: Improving hepatocyte pooling, activity and lab efficiency

Aired:  27 September 2018

Presenter:  Chris Bohl, Ph.D., Global Technical Support Manager

CryostaX® hepatocytes are created using a patented process that produces unique single-donor cell pellets. This format allows for distinct benefits to hepatocyte performance, efficiency in the lab, and test system design, precipitating the potential discontinuation of cryopreserved hepatocytes prepared from traditional methods. This webinar will discuss the technology, its optimal utilization and benefits...

Key concepts discussed in this webinar will include:
  • How single-freeze hepatocyte pellets preserve higher metabolic activity, longer
  • The benefits of skipping the thaw step
  • Pellet pooling versatility (demographics for human pools; larger rodent lot sizes)
  • Patented cryopreservation technology overview

About CryostaX:
CryostaX® patented hepatocyte technology makes using cryopreserved hepatocytes easier, more robust, and more efficient. Easier because you no longer need to thaw the vial of hepatocytes in a traditional water bath. Simply pour loose pellets into the thawing medium and spin. Higher metabolic activity pools because CryostaX technology allow the creation of fully customizable pools that have undergone only a single cryopreservation step, leading to less cryoinjury. More efficiency in the hood/bench because hepatocyte thaw variability is decreased and you are able to customize pools with specific demographics for your work. CryostaX hepatocytes come in all commonly used hepatocyte formats, are customizable (at no additional cost) for assured minimal yield per individual donor vial, and feature fast turnaround (in your hands in approx. 3-4 business days).

Challenges & Solutions In Today’s In Vitro Transporter Research Landscape

Aired:  20 June 2018

Presenter: Joanna Barbara, Ph.D., Sekisui XenoTech Vice President of Scientific Operations

Key concepts discussed in this webinar included:
  • Ramifications of recent FDA in vitro DDI guidance changes to transporter study designs
  • Challenges from diverse compounds in otherwise straightforward assays
  • Solutions to problems associated with specific compound characteristics
  • Case studies of problematic observations or data and the creative methods of troubleshooting applied

In vitro drug transporter inhibition and substrate potential assays as well as general cell permeability studies are performed at various stages of drug development to answer myriad questions. They can range from simple permeability screens to kinetic assessments in specialized cell systems using complex assay formats. 

Drug transporter assays are many and varied because numerous transporter proteins require evaluation, and study designs are usually based around the availability of an appropriate test system to study the transporter protein(s) in question. In general, experiments are conducted using polarized or transfected cell lines, hepatocytes or membrane vesicles. Each test system requires appropriate assay conditions and controls in order to generate useful data. 

Recent changes to the FDA in vitro DDI guidance document have emphasized the need for more considered transporter study designs to better inform in vivo expectations for drugs in development. The 2017 guidance explicitly recommends consideration of the impact of factors such as stability in the test system, non-specific binding to cells and experimental apparatus and other compound-specific characteristics in study conduct and data interpretation. Since assay designs are limited by individual test system assay needs, practically, this requires study designs to be augmented with careful monitoring and troubleshooting at assay and data interpretation stages when unexpected observations are made.

In this webinar, challenges associated with some diverse compounds in what should have been straightforward in vitro transporter assays will be examined. The discussion will focus on cell-based assays and the solutions applied to problems associated with specific compound characteristics, with a progressive analysis of increasingly complex case studies. Case studies will explore the problematic observations or data, creative methods of troubleshooting applied, and how we can learn from those experiences to better understand and address surprises in future transporter studies.

Patient-Derived Tumor Organoids for Personalized Medicine & Targeted Drug Discovery

Aired:  30 May 2018

Presenter: Motoki Takagi, Ph.D., Professor, Medical-industrial Translational Research Center, Fukushima Medical University

Patient-derived tumor organoids (PDOs) are cell aggregates produced by in vitro cell cultures of tumor tissue resected from patients. It is thought that PDOs better represent characteristics of tumor tissues in human body than ordinary cell lines. Therefore, they are considered as a more effective tool for the elucidation of cancer mechanisms and evaluation of anti-cancer agents. During the Fukushima Translational Research project*, PDOs were determined to be more similar to clinical tumor samples than ordinary cell lines in terms of gene expression profiling and thusly were coined as Fukushima PDOs (F-PDOs). This webinar is designed to introduce F-PDOs and present their features as well as the evaluation results of anti-cancer agents using F-PDOs.  

Key concepts discussed in this webinar will include:
  • Establishment and features of F-PDO
  • Difference between F-PDO and other PDOs
  • Anti-cancer drug evaluation using F-PDO
  • Advantages of F-PDO on PDX mouse development
*The Fukushima Translational Research project (Fukushima Project) was launched as part of the post-Great East Japan Earthquake reconstruction measures supported by the Ministry of Economy, Trade and Industry. The goal of the Fukushima project is to maximize the utilization of rare and trace biological samples by facilitating optimal:
  • Conversion into information
  • Sample processing and production of pathological models
  • Analytical technique development for ultratrace samples
  Registrants will be able to submit questions during registration as well as after viewing the webinar. Questions that weren't answered during the webinar will be responded to by email after the event.