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:
- Access to ApconiX scientists who will tailor our service specifically to your needs and better advise you on your next steps
- High quality ion channel profiling matched to your design-make-test cycle
- An average turnaround time for hERG data of less than 4 days following receipt of customer compounds
Our services include:
- Ion channel screening for hERG, cardiac and neuro liabilities, and all elements of the CiPA paradigm including the ion channel panel (hERG, hNav1.5 peak and late current, hKvLQT1, hKv4.3, hCaV1.2, hKir2.1), in silico action potential modelling, and investigation in hiPSC-cardiomyocytes
- Bespoke assay and cell line development
- Expertly performed direct functional electrophysiology measurements with fewer artefacts than ligand-binding or fluorescence assays
- Testing by manual patch-clamp or on the latest generation automated electrophysiology platforms (QPatch II and Patchliner) with the capacity for large numbers of compounds
Investigating Cardiac Liability
Inhibition of cardiac ion channels can adversely affect heart function and negatively impact a drug’s probability of success, value and competitiveness. By working with ApconiX you will benefit from our combined expertise in ion channel electrophysiology and project toxicology to move molecules away from this liability through informed choices in molecule design.
Our electrophysiology experts will rapidly generate high-quality hERG screening data for your drug discovery programme with over 80% of our hERG data returned to clients within one week.
Here’s which ion channels are routinley screened in the pharma industry (Authier et al., 2017):
NaV1.5 is cardiac sodium channel, CaV1.2 is cardiac “L-type” calcium channel, kvLQT1 is cardiac lks current
Refine your decision making with a deeper understanding of the potential for effects on cardiac safety to deliver an optimal and de-risked clinical candidate. ApconiX routinely offer sodium and calcium channel assays for a more comprehensive assessment of cardiac liability. On a case-by-case basis we can also deploy other cardiac ion channel assays to suit your needs including cardiac ‘T-type’ calcium channels and Kv1.5 as well as 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 partner, PhysioStim.
Given over 500 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 partners 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 and we will support you to make the right decision
Assay Development
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:
Hit identification/HTS
We have 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 and hits were confirmed by automated electrophysiology.
Selectivity profiling
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.
Bespoke investigations
Whether we are testing testing pharmaceuticals or agrochemicals, we are happy to carry out bespoke investigations to help you optimise your discovery programme. For example, we have investigated the effect of impurities, compound solubility and new modalities such as antibodies, peptides and aptamers.
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 solvents, 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.
