Selective OXER1 Antagonist
Selective Oxo-eicosanoid receptor 1 (OXER1) Antagonist
We are developing an oral, selective OXER1 antagonist candidate. OXER1 is a G protein-coupled receptor (GPCR) that is highly selective for 5-Oxo-eicosatetraenoic acid (5-oxo-ETE), a potent human eosinophil chemo-attractant.1 Migration of eosinophils to body sites including the skin, lungs and intestines is mediated by eosinophil chemo-attractants such as 5-oxo-ETE. Eosinophils play a key role in Type 2 inflammation-driven diseases, including skin, respiratory and gastro-intestinal diseases.
Eosinophilic-related diseases represent a significant area of unmet need in global health. Several biologics have been approved for the treatment of eosinophil-related diseases. Several of the approved monoclonal antibody treatments for severe eosinophilic asthma are currently in clinical trials aimed at expanding their indications to include other eosinophilic disorders. Compared to approved biologics, small molecule OXE receptor antagonists may offer a promising and potentially a more cost-effective treatment of eosinophilic-driven disorders.
Our Selective OXER1 Antagonist Program
The OXER1 antagonist program is based on the research of Dr. William Powell, Professor Emeritus in the Department of Medicine at McGill University, working in collaboration with Dr. Joshua Rokach of the Florida Institute of Technology. Dr. Powell serves as an advisor to Liminal BioSciences on the OXER1 antagonist program.
In addition to our experienced in-house medicinal chemistry group, we have a strong understanding and well-established, in-house expertise in GPCR biology.
Our OXER1 antagonist program is currently at the pre-clinical stage.
- Bäck, M et al., Br. J. Pharmacol. (2014), 171: 3551 – 3574
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- 5-Oxo-ETE receptor antagonists
- Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7
- Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid
- 5-Oxo-ETE and the OXE receptor
- Targeting the OXE receptor as a potential novel therapy for asthma
- Inhibition of allergen-induced dermal eosinophilia by an oxoeicosanoid receptor antagonist in non-human primates
- Novel highly potent OXE receptor antagonists with prolonged plasma lifetimes that are converted to active metabolites in vivo in monkeys
- Inhibition of 5-oxo-6,8,11,14-eicosatetraenoic acid-induced activation of neutrophils and eosinophils by novel indole OXE receptor antagonists