Selective OXER1 Antagonist
Selective Oxo-eicosanoid receptor 1 (OXER1) Antagonist
We are developing a selective OXER1 antagonist aimed at treating eosinophilic driven diseases. 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. Migration of eosinophils to body sites including the skin, lungs and intestines is mediated by eosinophil chemo-attractants such as 5-oxo-ETE. Eosinophils are involved in acute and chronic inflammation and play an important role in a large number of allergic, inflammatory and proliferative diseases, such as skin, respiratory diseases and gastro-intestinal diseases, such as asthma, allergic rhinitis, chronic obstructive pulmonary disorder, atopic dermatitis, psoriasis and acne.
Eosinophils are major effector cells in the immune system. They are part of the innate immune system; traditionally recognized as the first line of defense against parasitic infections. Eosinophils themselves are key in mounting an appropriate immune response against pathogens. When activated, they release a cocktail of toxic proteins (to damage the parasite), along with cytokines to attract other immune cells. However, when eosinophils are chronically activated, these toxic proteins can also damage normal tissue and promote inflammation. Eosinophils are also recruited from the blood into the tissues at the sites of inflammation. They also play a role in tissue repair and resolution of inflammation.
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 a broader range of eosinophilic disorders. Compared to approved biologics, small molecule OXE receptor antagonists may offer a promising and potentially more cost-effective option for 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 discovery program is currently at the preclinical stage. We are targeting selecting a lead candidate for further development in the first half of 2023.
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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