High-Throughput Screening Assay Services
Aurora Biomed provides functional assay services on an exclusive, out-sourced basis.We are currently carrying out assay services for various ion channel targets including hERG safety screen. Several options for these services exist, we can read/test flux assay samples from your experiments on ICR, we can screen your compounds/library in our laboratories or we can accept cell lines to develop assay for you as part of our services.
Aurora Biomed has a team of highly trained molecular biologists have a solid understanding of ion channels and cold flux assays. We enjoy a challenge and feel confident in providing solutions to further your ion channel screening needs.
We are pleased to offer both cold flux assay services using our proprietary Ion Channel Reader technology and manual voltage-clamp electrophysiology assays.
Cold flux assays utilize tracer ions to study the ion channel of interest. The method of detection for Aurora Biomed’s cold flux assays is flame atomic absorption spectroscopy as employed by our proprietary Ion Channel Reader technology. The Ion Channel Reader Series provides a high throughput format for ion channel screening by the flux assay approach. The use of high throughput assays helps reduce the burden on electrophysiology by providing some idea of which compounds should be screened if resources are limited and not all compounds can be screened with manual-patch clamp. The cold flux assay approach is ideal for determining which compounds to follow up with electrophysiology as there is a strong linear correlation (R=0.88) and consistently identical drug rank orders between the two methods.
Manual voltage-clamp electrophysiology is the gold-standard for ion channel screening. Moreover, the FDA requires in vitro electrophysiology studies in conjunction with in vivo studies for compounds submitted for NDA status. Oocyte-based studies assess potential cellular mechanisms that may not be evident from in vivo data.
Cardiac Safety Services
QT Prolongation and Drug Discovery
The assessment of potential leads for liability to QT prolongation is an essential process in the field. Although many researchers use measurement of ionic currents through hERG (IKr) channels as a primary safety assessment screen, there has been no conclusive evidence of the predictive value of these screens in clinical testing. Adopting in vivo QT measurement studies at an early stage in the discovery process would yield important information on the potential of compounds for QT prolongation in humans. The benefit is that QT-prolonging compounds are removed early from the discovery pipeline. Conversely, more time and resources are devoted to those compounds not prolonging QT.
In Vivo QT Measurement in Beagle Dogs
Aurora Biomed offers non-GLP QT measurement studies in order to assess the torsadogenic (QT prolonging) nature of compounds in conscious beagle dogs.
hERG Assay Services
Screening for QT-Prolongation due to hERG Inhibition
The hERG potassium channel conducts rapidly activating delayed rectifier K+ currents that critically contribute to cardiac repolarization. Mutations in the hERG gene and drug-induced blockde of Ikr currents have been linked to delayed repolarization of action potential resulting in prolonged QT interval. QT prolongation can lead to potentially lethal torsade de pointes, a form of polymorphic ventricular arrythmia. It is for this reason that inhibition of hERG is considered a significant risk factor against cardiac safety of new drugs. Moreover, the FDA recommends that all new drugs be evaluated for long QT using cloned ion channels as the targets for pre-clinical studies. The hERG channel assay is performed using our CHO/hERG cell line. (cell-line licensing fee not required).
Kv1.3 Assay Services
Kv1.3 is a voltage gated channel which is upregulated in fully differentiated autoreactive T-cells. Modulation of this channel is being explored as a therapeutic strategy for various autoimmune diseases including multiple sclerosis, type I diabetes, and rheumatoid arthritis. The Kv1.3 channel assay is performed using our CHO/Kv1.3 cell line. (cell-line licensing fee not required)
Nav1.5 Assay Services
Mutations in the SCN5a gene are responsible for different clinical phenotypes - the LQT3 variant of long QT syndrome (LQTS), Brugada syndrome and progressive cardiac conduction defect. Moreover, drug blockade of Nav1.5, in addition to hERG, has been linked to prolonged QT interval. This finding has compelled some pharmaceutical companies to add Nav1.5 to their cardiac safety suite of ion channel assays. (cell-line licensing fee required)
Stretched Activated Channel Services
Calcium Channel Services
These channels are involved in many cellular functions, such as muscle contraction, neurotransmitter and hormone secretion, neuronal excitability, and gene expression. The development of a large number of drugs like ziconotide, verapamil, and nifedipine against hypertensions and other targets, exemplifies their clinical relevance. Calcium channels are composed of several subunits.
Nak-ATPhase Assay Services
The Na/K pump regulates the movement of potassium ions into and sodium ions out of cells thereby maintining an ionic gradient and contributing to membrane potential. Na/K-ATPase function is involved in physiological processes such as action potential generation, regulation of cell volume, and the assembly of tight junctions in epithelial cells. Na/K-ATPase is a therapeutic target for diseases such as cancer, ischemia, hypertension, hyperthyroidism, and polycystic kidney disease. Screening is available for α1, α2 & α3 subunits (cell-line licensing fee not required)
Customized Assay Services
For more information and quotation request, please send email to email@example.com
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