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Using high-throughput automated patch clamp electrophysiology to identify novel TREK-1 modulators in an animal venom library

We developed a high-throughput, electrophysiological assay of TREK-1 function to identify novel modulators. The assay was optimized to identify both activators and inhibitors, providing comprehensive mechanistic data for high value, limited supply screening libraries, such as the venom fraction library used in this study (Targeted Venom Discovery Array, T-VDA, Venomtech, UK).

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Scientifica PatchScope Pro: an integrated calcium-imaging and patch-clamp system suitable for selecting specific subsets of neurons for electrophysiology recordings

Scientifica’s PatchScope Pro is an integrated electrophysiology rig incorporating an inverted phase-contrast fluorescence microscope, motorised XY stage and PatchStar micromanipulators, suitable for patch-clamp recording.

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Fluorescence-based drug repurposing screen of the potassium channel, KV3.1 with V434L mutation

KV3.1 is a voltage-gated potassium channel encoded by the KCNC1 gene. Mutations in the KV3.1 protein can manifest as a variety of neurological disorders including myoclonic epilepsy and ataxia due to K+ channel mutation (MEAK), developmental epileptic encephalopathy (DEE), or hypotonia.

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Development of TRPML1-4A assays across manual, automated patch-clamp, and fluorescence-based platforms

We developed a suite of screening assays using manual patch-clamp, automated patch-clamp and fluorescence-based platforms capable of identifying modulators of the TRPML1-4A channel.

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GLP hERG assay validation following ICH E14/ S7B 2022 Q&A best practice guidelines

The recently released ICH E14/S7B 2022 Q&As provides the best practice guidelines for evaluating the effect of preclinical compounds on the human ether-à-go-go-related gene (hERG) potassium channel1.

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Development of a manual patch-clamp assay to characterise native endo-lysosomal ion channels

Lysosomes are a critical component of eukaryotic cells, playing a role in degradation and recycling processes, signal transduction and extracellular secretion(I). Ion channels expressed on the endo-lysosomal membrane are crucial in intracellular signalling and maintaining the acidic luminal pH for optimal hydrolase activity(II). There are a number metabolic disorders, known as lysosomal storage diseases, that arise from lysosomal dysfunction(III).

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Rescue of defective CFTR (dF508) is enhanced by targeting the ubiquitin proteasomal system

The dF508 mutation represents the most common cause underlying cystic fibrosis. The resultant misfolding of the nascent cystic fibrosis transmembrane regulator (CFTR) protein and its subsequent proteasomal degradation lead to a deficiency in functional CFTR channels and Cl- efflux at the apical cell membrane in ducts throughout the body (Veit et al. 2016).

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Development and validation of a Qube automated patch clamp hERG assay at physiological temperatures

The development of Automated Patch Clamp (APC) technology over the last 20 years has
transformed the research and development process for identifying novel drugs for ion channel targets.

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Inhibition of hERG by siRNA Takes More Than 8 hrs to Manifest: Implications for Designing hERG Assays

Nonclinical safety pharmacology studies for siRNA follow a hybrid of the small molecule (SM) guidance and biologics guidance. The Oligonucleotide Safety Working Group (OSWG) has published a series of recommendation papers for oligonucleotides, including recommendations for safety assessment, because development of oligonucleotide-based therapeutics is not addressed by regulations. This is especially true regarding the hERG assay, which is a core assay in ICH S7B for SM. While OSWG states that a hERG study is not necessary for IND submission, all approved siRNAs have submitted hERG data which are necessary for requesting a TQT waiver.

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Validation of an ASIC1a ligand-gated assay on an automated patch-clamp platform and it’s use for novel ligand screening

There is growing interest in automated patch-clamp (APC) assays for ligand-gated targets which are expressed throughout the peripheral and central nervous system. The Acid-Sensing Ion Channel (ASIC) family comprises combinations of ASIC1-4 proteins that form acid-activated cation-selective channels.

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