Comprehensive Assay Collection for TMEM175 Drug Discovery

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TMEM175 as a Target for Drug Discovery

TMEM175 is a lysosomal ion channel that functions as both a proton channel and potassium channel. It plays a crucial role in maintaining lysosomal pH, and is essential for lysosomal function. Mutations in TMEM175 lead to impaired lysosomal degradation and increased neuronal susceptibility to alpha-synuclein aggregation, and are associated with an increased risk of developing Parkinson’s disease.

Validated TMEM175 Assays

Gain exclusive insights for your Parkinson’s disease pipeline with our suite of proprietary assays to identify TMEM175 inhibitors and activators. Our TMEM175 services are supported by the most expansive collection of HTS assays to deliver valuable information about how your compounds interact with this disease relevant lysosomal target. All assays generate EC50 values in line with literature reported values for known tool compounds, ensuring data reliability from day to day. Our validated cell line and robust assay platforms can be leveraged to assess what you need, from ion permeability profiling to inhibitor identification.

If you’re searching for TMEM175 variants or additional readouts to support your research, our team can help.

Thallium-free Potassium Channel Assay

Proprietary ION technology that measures potassium efflux through activated TMEM175 channels expressed on the plasma membrane in real time. DCPIB and 4-AP are used to demonstrate a robust hit identification capability. The measurement of potassium yields physiologically relevant data for TMEM175 when compared to other surrogate readouts.

TMEM175 potentiator assay results displaying a dose response of DCPIB that uses the Thallium-free potassium channel assay.

Brilliant Thallium Assay

Gold standard for potassium channel drug discovery. Thallium acts as a surrogate for potassium ions to probe TMEM175 channel activity. This solution is able to identify activators and inhibitors of TMEM175, but requires longer compound incubation times to generate a robust response.

TMEM175 potentiator assay results displaying a dose response of DCPIB that uses the Brilliant Thallium Snapshot potassium channel assay.

Brilliant Thallium Snapshot Assay

Proprietary ION technology that measures thallium efflux in response to TMEM175 activation. This assay produces the largest screening window of all available assays, and can be used to identify activators or inhibitors. TMEM175 activation is visualized in real time upon stimulation with DCPIB.

Brilliant Intracellular pH Assay

Measures proton transport through TMEM175 upon activation with DCPIB. As a predominantly proton channel on its native lysosomal membrane, this physiologically relevant readout can help you identify compounds that alter the proton conductance of TMEM175.

TMEM175 potentiator assay results displaying a dose response of DCPIB that uses the Brilliant Intracellular pH assay.

Lysosomal TMEM175 Assays

Powered by our Halotag-compatible thallium indicator collection, we’ve enabled HTS of TMEM175 activity expressed on lysosomal membranes inside viable, intact cells. Available in 384-well plate formats for high-throughput drug discovery campaigns. No lysosomal manipulation or isolation required. Probe TMEM175 in its native membrane and environment to get the most relevant insights into target engagement and TMEM175 pharmacology.

Lysosomal Thallium Flux Assay

Our proprietary thallium dye is localized to the lumen of lysosomes to measure thallium flux across the lysosomal membrane in intact cells. Enables the identification of activators, such as DCPIB, and inhibitors, like 4-AP, of lysosomal TMEM175 using standard HTS methods (384-well format).!

Fluorescence image showing ION Thallos Gold-HTL localized to lysosomes inside of viable cells.

ION Thallos Gold-HTL loaded lysosomes

Lysosomal TMEM175 potentiator assay results displaying kinetic traces and a corresponding dose response curve of DCPIB that usesour organellar ion channel assay platform.

Sample activator and inhibitor data using our lysosomal drug discovery platform for TMEM175 assays. Included data are normalized kinetic traces (top left), a dose response curve to DCPIB (top right), and a dose response curve to 4-AP in TMEM175 expressing cells and wild-type cells (bottom left).

Lysosomal TMEM175 inhibition assay results displaying a dose response curve of 4-AP that uses our organellar ion channel assay platform.

Lysosomal Proton Flux Assay

In development.

Summary

Whether you are screening for TMEM175 modulators or exploring unique pharmacology, our TMEM175 platform offers proprietary insights, maximum throughput, readout flexibility, and physiologically relevant data to support your discovery needs.

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