Orexin Family Related Drug Discovery Products
Membrane proteins are the most successful class of therapeutic targets. Creative Biolabs has developed a comprehensive collection of membrane protein in vitro assays for drug discovery that cover most membrane protein targets.
Creative Biolabs has the assays you can rely on for high throughput screening, lead optimization, characterizing and discovering targets, and uncovering the complexity of disease pathways. We can offer membrane protein in vitro assay kits that save valuable laboratory time and is ideal for high throughput screening.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
A group of neurons in the hypothalamus that surrounds the fornix and extends over the lateral hypothalamus create the orexin peptides. Orexin-producing neurons range in number from 50,000 to 80,000 in the human brain, and these cells have wide projections to numerous brain areas. The orexin neurons directly project to the cortex and also innervate cholinergic and noncholinergic neurons in the basal forebrain. The orexin system is well positioned to coordinate the activation of numerous neuronal systems involved in diverse aspects of arousal through these projections.
As a leader in drug discovery, Creative Biolabs offer our clients a series of orexin family drug discovery in vitro assays and products with the best quality:
Overview of Orexin Family
- HCRTR1 (OX1R)
Constitutive OX1R knockout mice are reported to have a moderate phenotype with observable sleep fragmentation, albeit a thorough description of these animals has not yet been published. Similar to this, acute OX1R-selective antagonism with a partially selective compound has little to no impact on the structure of sleep, and this compound's off-target activities may prevent its use in dose-response studies to exposures that may be necessary to observe effects on polysomnography with the compound alone. Furthermore, it has been shown that this substance boosts dopamine levels in the prefrontal cortex and dampens the effects of an OX2R-selective antagonist.
Fig.1. Relationship between orexin and sleep.1,2
- HCRTR2 (OX2R)
OX2R is preferentially expressed above OX1R in the histaminergic neurons of the TMN, despite the fact that both orexin receptors have largely overlapping expression across the brain. Input from orexin-secreting neurons is a primary source of information for TMN neurons, which are typically active throughout waking hours and gradually become less active during NREM and REM sleep, virtually mirroring orexinergic activity. The prefrontal cortex, thalamus, and other subcortical areas receive extensive projections from neurons of the TMN, which is the brain region where HA signaling is mostly produced.
Orexin Family Drug Discovery
For the development of small molecule medicines controlling arousal for the treatment of insomnia, EDS, narcolepsy, and mental disorders related to sleep/wake dysregulation, orexin receptors constitute an alluring and well-validated target. Initial tool compounds have been crucial in identifying the role of orexins and their corresponding receptors in mechanisms controlling arousal and alertness state as well as other behaviors connected to reward processing, nociception, anxiety, and mood disorders. These approaches have been used in conjunction with genetic approaches. Targeting orexin signaling for the treatment of insomnia has now received clinical proof of concept, offering mechanistic difference from the existing standard of care. This has been made possible by the creation of clinically effective drugs.
References
- Wang, Chunmei, et al. "The orexin/receptor system: molecular mechanism and therapeutic potential for neurological diseases." Frontiers in molecular neuroscience 11 (2018): 220.
- Distributed under Open Access License CC BY 4.0, without modification.
