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Papers of the Week

Papers: 7 Jan 2023 - 13 Jan 2023

Pharmacology/Drug Development

2023 Jan 09

J Med Chem

Discovery of , a Selective CNS Penetrant Chemical Probe as Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonist.


Mesch S, Walter D, Laux-Biehlmann A, Basting D, Flanagan S, Miyatake Ondozabal H, Bäurle S, Pearson C, Jenkins J, Elves P, Hess S, Coelho A-M, Rotgeri A, Bothe U, Nawaz S, Zollner TM, Steinmeyer A
J Med Chem. 2023 Jan 09.
PMID: 36622903.


Transient receptor potential ankyrin 1 (TRPA1) is a voltage-dependent, ligand-gated ion channel, and activation thereof is linked to a variety of painful conditions. Preclinical studies have demonstrated the role of TRPA1 receptors in a broad range of animal models of acute, inflammatory, and neuropathic pain. In addition, a clinical study using the TRPA1 antagonist GRC-17536 (Glenmark Pharmaceuticals) demonstrated efficacy in a subgroup of patients with painful diabetic neuropathy. Consequently, there is an increasing interest in TRPA1 inhibitors as potential analgesics. Herein, we report the identification of a fragment-like hit from a high-throughput screening (HTS) campaign and subsequent optimization to provide a novel and brain-penetrant TRPA1 inhibitor (compound ), which is now being made available to the research community as an open-source in vivo probe.