omigapil

Omigapil is a small molecule neuroprotective agent originally developed by Novartis and later advanced by Santhera Pharmaceuticals. It is structurally related to selegiline but does not inhibit monoamine oxidase (MAO) activity. Omigapil acts as an anti-apoptotic compound, primarily inhibiting programmed cell death (apoptosis) through interaction with the enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). By preventing S-nitrosylation of GAPDH, it blocks the binding of GAPDH to the ubiquitin ligase SIAH1 and subsequent nuclear translocation, thereby inhibiting downstream pro-apoptotic signaling pathways. Omigapil has demonstrated neuroprotective effects in preclinical models and was investigated for use in conditions such as congenital muscular dystrophy (CMD), Parkinson's disease, amyotrophic lateral sclerosis (ALS), and motor neuron disease. Despite promising safety data in pediatric CMD patients, clinical development has been discontinued following phase I/II trials due to lack of efficacy or strategic decisions[3][4][5][8].

Other names

omigapil [INN]N-(benzo[b][1]benzoxepin-5-ylmethyl)-N-methylprop-2-yn-1-amine