# Expanding the Chemical Biology of K2P Channels with Selective Cellular and In vivo Probes

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $473,430

## Abstract

Project Summary
The long-term goals of this project are to develop new small molecules that can be used to control K2P
potassium channel function and that will be able to label K2P channels so that they can be imaged in cells and
in vivo. K2Ps are responsible for ‘leak’ potassium currents that are pivotal in modulating the excitability of
neurons. Members from this diverse potassium channel family respond to varied stimuli that include pH
changes, temperature, and mechanical force. K2P channels have well-established roles in the nervous and
cardiovascular systems and are implicated in pain, anesthetic responses, thermosensation, and mood, but
remain the least well-understood potassium channel class. Ion channels are highly desirable drug targets as
they are readily accessible to extracellular compounds and their modulation brings about rapid changes in
excitable cell function in the heart and brain. Nevertheless many channels, including all K2P family members,
lack pharmacological agents that can selectively affect function. This lack of pharmacological control creates a
serious deficiency in our ability to understand, probe, and impact K2P in vivo function. We seek to address this
fundamental gap by building on recent discoveries from our laboratory that define a novel small molecule
binding site in the mechano- and thermo-sensitive TREK K2P subfamily that is important for pain, analgesic
responses, and mood. We will leverage a multidisciplinary approach that includes structure-guided small
molecule design together with structural and electrophysiological measurements to create new, selective
chemical agents that can be used to probe K2P activity. Because of their important roles in human physiology,
K2Ps are targets for drugs for the treatment of chronic pain, stroke, and depression. Thus, developing new
small molecules that affect K2P channel function should not only provide powerful tools for dissecting in vivo
activity of K2Ps but should aid in the development of new therapeutic agents for a range of human diseases.

## Key facts

- **NIH application ID:** 9856485
- **Project number:** 5R01MH116278-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** DANIEL L MINOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,430
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856485

## Citation

> US National Institutes of Health, RePORTER application 9856485, Expanding the Chemical Biology of K2P Channels with Selective Cellular and In vivo Probes (5R01MH116278-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856485. Licensed CC0.

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