# Discovery of NaV1.7 Inhibitors for the Treatment of Pain

> **NIH NIH U44** · SITEONE THERAPEUTICS, INC. · 2020 · $461,907

## Abstract

PROJECT SUMMARY
The objective of our program is to develop a safe and effective nonopioid analgesic for the treatment of
neuropathic pain, such as pain associated with chemotherapy-induced peripheral neuropathy, that targets an
isoform of the voltage-gated sodium ion channel, NaV1.7. Voltage-gated sodium channels are involved in the
transmission of nociceptive signals from their site of origin in the peripheral terminals of DRG neurons to the
synaptic terminals in the dorsal horn. Ten mammalian isoforms exist, NaV1.1–1.9 and NaX. NaV1.7 is the
most abundant tetrodotoxin-sensitive sodium channel in small diameter myelinated and unmyelinated
afferents, where it has been shown to modulate excitability and set the threshold for action potentials. Humans
lacking functional NaV1.7 due to a rare genetic condition are unable to experience almost all types of pain.
Efforts to develop systemic inhibitors of NaV1.7 have been complicated by the challenge of achieving
selectivity over other NaV isoforms expressed in the diaphragm, phrenic nerve, heart and central nervous
system that are critical for safety. SiteOne Therapeutics has discovered a series of potent, state-independent
NaV1.7 inhibitors that exhibit >1000-fold selectivity over other human isoforms. Work conducted under this
program will support advancement of a lead candidate into clinical development as a therapeutic for
neuropathic pain.

## Key facts

- **NIH application ID:** 10130382
- **Project number:** 5U44NS111779-02
- **Recipient organization:** SITEONE THERAPEUTICS, INC.
- **Principal Investigator:** John Vincent Mulcahy
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $461,907
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130382

## Citation

> US National Institutes of Health, RePORTER application 10130382, Discovery of NaV1.7 Inhibitors for the Treatment of Pain (5U44NS111779-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130382. Licensed CC0.

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