ox2 receptor

EMPA is a selective, high-affinity and reversible antagonist of orexin OX2 receptor(human and rat OX2-HEK293 membranes with KD values of 1.1 and 1.4 nM respectively)

Iptacopan (LNP023) is an inhibitor with high affinity to factor B, with a KD value of 7.9 nM and an IC50 value of 10 nM.

SB-674042 is a potent, selective dual antagonist of the non-peptide orexigenic peptides OX1 and OX2 receptors, with IC50 values of 3.76 nM and 531 nM, respectively. SB-674042 is suitable for the treatment of depression.

OX2R-IN-2 (compound 63c) is an agonist of the type 2 orexin receptor (OX2R) with an EC50 value of 339 nM. It can cross the blood-brain barrier and exhibits no cytotoxicity.

Ledasorexton (Example 1) is an orally active OX2R agonist with an EC50 of 0.99 nM and exhibits arousal effects.

Potent and selective orexin OX2 receptor agonist (EC50 = 28 nM at human OX2 expressed in CHO cells). Displays approximately 100-fold selectivity for OX2 over OX1 (EC50 = 2.75 μM at human OX1 expressed in CHO cells). Depolarizes OX2-expressing histaminergic neurons in mouse brain slices. Increases wake time in wild type mice. Suppresses cataplexy-like symptoms in OX knockout mice. Nagahara et al (2015) Design and synthesis of non-peptide, selective orexin receptor 2 agonists. J.Med.Chem. 58 7931 PMID:26267383 |Irukayama-Tomobe et al (2017) Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models. Proc.Natl.Acad.Sci.USA. 144 5731 PMID:28507129

MK-1064 (Urokinase inhibitor 1) is a selective orexin 2 receptor antagonist (2-SORA).

TCS-OX2-29 is a potent and selective OX2 receptor antagonist (IC50: 40 nM). It displays >250-fold selectivity for OX2 over OX1.

Orexin receptor antagonist 4 is potent and selective orexin 2 receptor (OX2R) antagonist. Orexin receptor antagonist 4 shows IC50 of 4.27 nM and 295 nM for OX2R and OX1R, respectively.

OX2R-IN-3 (Compound 53) functions as an orally active agonist for the type 2 orexin receptor (OX2R), exhibiting an EC50 value of less than 100 nM [1].

OX-201 is a selective agonist for OX2R with an EC50 of 8 nM. Pathological proteins produced by neurons are released into the interstitial fluid (ISF) in a neural activity-dependent manner and subsequently cleared from the brain via lymphatic pathways. The efflux of these proteins to the ISF correlates with the wakeful state of neurons. OX-201 can induce neuronal awakening and enhance the release of tau into the hippocampal ISF. While it does not alter hippocampal tau levels, OX-201 has potential applications in Alzheimers disease (AD) related to sleep/wake cycle disturbances.

JNJ-54717793 is an orally active, brain-penetrating compound that acts as a selective and high-affinity antagonist of the orexin-1 receptor (OX1R) with a plasma EC50 of 85 ng/mL. It demonstrates K_i values of 16 nM for hOX1R (human OX1R) and 700 nM for hOX2R, indicating its strong preference for hOX1R over hOX2R. JNJ-54717793 is recognized for its effectiveness in the treatment of anxiety disorders.

Orexin B, rat, mouse Acetate (Rat orexin B) is an endogenous agonist at Orexin receptor with Kis of 420 and 36 nM for OX1 and OX2, respectively.

Seltorexant (JNJ-42847922) crosses the blood-brain barrier and quickly occupies OX2R binding sites in the rat brain. Seltorexant is a high-affinity and selective orexin-2 receptor antagonist (pKi: 8.0 and 8.1 for human and rat OX2R).

Filorexant (MK-6096) is an orally bioavailable, effective, and selective reversible antagonist of OX1 and OX2 receptors, with (Ki <3 nM).

MK-3697, an isonicotinamide small molecule, acts as a potent and selective Orexin 2 receptor antagonist (Ki: 0.95 nM).

Rocavorexant is an antagonist of the orexin-1 receptor (orexin-1 receptor), exhibiting a pIC50 value of 9.1 for human OX1 and a pIC50 of 6.0 for human OX2.

Orexin 2 Receptor Agonist 3 is an orally active and brain-penetrant agonist of the orexin receptor 2 (OX2) with an EC50 value of 2.5 nM. This compound increases wakefulness in both orexin/ataxin-3 NT1 mouse models and healthy Beagle dogs. It is applicable for research related to narcolepsy.

OX2 receptor antagonist

Almorexant (ACT 078573) is a potent and competitive dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM for OX1 and OX2, respectively.

TCS 1102 is an effective, dual orexin receptor antagonist (Ki: 0.2/3 nM for OX2/1 receptors).

YNT-185 is a nonpeptide, selective agonist of the orexin type-2 receptor (OX2R), with EC50 values of 0.028 μM for OX2R and 2.75 μM for OX1R. Additionally, YNT-185 effectively alleviates symptoms of narcolepsy-cataplexy in mouse models.

TCS-OX2-29 is a selective orexin-2 receptor antagonist (IC50 = 40 nM), which plays an important role in pain modulation.

SB-649868 (GSK649868) is a potent and selective orally active antagonist of orexin(pKi =9.4 and 9.5 at the OX1 and OX2 receptor, respectively).