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Ion Channel Screening
Whether you want to explore an ion channel as a potential new target or understand cardiovascular liability, or other liabilities, ApconiX can help you with our electrophysiology expertise, customer-focused flexibility and rapid delivery of high data quality. The services we offer include hERG screening and CiPA assays, complemented by a wide range of assay development and ion channel screening services.
“Your data turnaround time is incredibly good and it really helps us track the SAR and progress our compounds in a rapid and efficient manner. Thanks ApconiX for your wonderful support to Bugworks.”
You will benefit from:
- Direct, functional electrophysiology measurements, performed by experts, with fewer artefacts than ligand-binding or fluorescence assays
- Testing on the latest generation automated electrophysiology platforms with the capacity for large numbers of compounds.
- Talking directly to an ApconiX scientist to tailor our service specifically to your needs and advice to take an informed next step.
- Rapid return of data to fit with your design – make – test cycle
Investigating Cardiac Liability
Inhibition of cardiac ion channels can adversely affect heart function leading to a significant negative impact on a drug’s probability of success, value and competitiveness. You will benefit from our combined expertise in ion channel electrophysiology and project toxicology that allows you to move molecules away from this liability while there are still choices in chemical design.
ApconiX offers you high-quality hERG screening data generated by our electrophysiology experts as part of your drug discovery programme. These data are generated and reported quickly – ApconiX reports over 80% of hERG data to clients within one week!!
Here’s what ion channels the Pharma industry routinely screens (Authier et al., 2017):
NaV1.5 is cardiac sodium channel, CaV1.2 is cardiac “L-type” calcium channel, kvLQT1 is cardiac lks current
ApconiX also offers a more comprehensive assessment of cardiac liability. Additional sodium channel and calcium channel assays are available routinely that give further insight. In addition, there are other cardiac ion channel assays we can deploy on a case-by-case basis to suit your needs, e.g. hERG trafficking, cardiac “T-type” calcium channel or Kv1.5. You will gain a deeper understanding of the potential for effects on cardiac safety to refine your decision-making and deliver an optimal (de-risked) clinical candidate.
We can also offer more advanced models of cardiac safety, such as Purkinje fibre, cardiac contractility and Langendorf models.
It is a regulatory requirement that an assessment of hERG inhibition should be made by manual patch-clamp to Good Laboratory Practise (GLP) standards. GLP-hERG is provided through our expert alliance partner, PhysioStim (visit the European Centre of Excellence page for more information).
Given over 300 years of combined expertise in drug discovery and safety, ApconiX is uniquely positioned to work with your project team to
interpret your data in the context of your drug discovery program.
Comprehensive in vitro Proarrhythmia Assay (CiPA)
The regulations regarding the testing of new drugs for cardiac safety are changing. ApconiX can help you understand how these new regulations will affect you and guide you through the testing process. We are working with a number of stakeholders to create this new regulatory framework called CiPA (Comprehensive in vitro Proarrhythmia Assay). The new paradigm will include the testing of a wider panel of ion channels, in silico modelling of ion channel data, and measurements using human stem cell-derived cardiomyocytes.
ApconiX offers a comprehensive CiPA assay package based on the seven CiPA ion channel targets proposed by CiPA:
- hERG, hNaV1.5 (peak current), hNaV1.5 (late current), hCaV1.2, hKir2.1, hKv4.3/KChip Ito current), and hKvLQT1/mink (Iks current).
- Through our expert alliances with QT Informatics and PhysioStim, ApconiX can also deliver CiPA in silico action potential modelling and measurements of human stem cell-derived cardiomyocytes.
- We are here to give you the advice you need to take an informed next step. We will support you to make the right decision.
Ion channels play a central role in normal and disease biology. ApconiX can develop and optimise novel ion channel assays for hit identification, selectivity profiling or mechanism of action studies. See some examples of our work below:
Developed a dual addition protocol in 384-well format for the high-throughput screen (HTS) of ~10,000 compounds against an epithelial sodium channel isoform. Cells were generated by baculoviral transduction of HEK cells with 95+% efficiency. Hits were confirmed by automated electrophysiology.
Defining the selectivity profile of compounds against a bespoke panel of ion channel targets. Each panel is specific to the client’s needs and the selectivity they are trying to demonstrate.
Flexibility and customer focus
Our clients may have known impurities in their test compound and need to understand the effect these may have in our assays. We are happy to investigate the effect of impurities in your preparations.
We also realise not all compounds are soluble in standard organic solvent, e.g. DMSO. Our clients are often looking for ways to increase the solubility of their compounds with a variety of organic and aqueous solvents. We are happy to try a number of solvents which have been validated in our assays.