ISC 17536 / Glenmark - LARVOL DELTA

Discovery of BAY-390, a Selective CNS Penetrant Chemical Probe as Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonist. (PubMed, J Med Chem) - "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 18, BAY-390), which is now being made available to the research community as an open-source in vivo probe."

Journal • Diabetic Neuropathy • Neuralgia • Pain

A randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of TRPA1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function. (PubMed, Pain) - "These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger Phase 2 study."

Clinical • Journal • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Musculoskeletal Pain • Neuralgia • Pain • Peripheral Neuropathic Pain

Transient receptor potential ankyrin 1 (TRPA1) antagonists: a patent review (2015-2019). (PubMed, Expert Opin Ther Pat) - "During this period, three new molecules entered the clinic (ODM-108, HX-100, and GDC-0334) bringing the total number of TRPA1 antagonists to reach clinical trials to five (including two earlier molecules, CB-625 and GRC 17536); however, to our knowledge, development of all five molecules have been discontinued. Further clinical trials of recent TRPA1 antagonists with good pharmacokinetics would be needed to help understand TRPA1 involvement in human diseases and its potential as a therapeutic target."

Journal • Asthma • Pain • Respiratory Diseases

Transient receptor potential ankyrin 1 (TRPA1) antagonists. (PubMed) - "Despite the clear progress, many unanswered questions remain. Future advancement to Phase 3 studies will assess the real translational potential of this research field."

Journal • Asthma • Biosimilar • Diabetes • Immunology • Inflammation • Pain