Anxiety disorders are the most common psychiatric illnesses. Present drugs can provide temporary relief for anxiety, however, they also come with side effects and safety concerns such as dependence, suicide, overdose and so on. Therefore, it is critical to discover new anxiolytic targets. An ongoing area of interest in the field of psychiatric diseases is the orexin system. Emerging body of evidences show that orexin receptor 1 (OX1R) has promising potential as novel anxiolytic target. However, little attention has been paid to orexin receptor 2 (OX2R) in anxiety. In this study, by using behavioral test, stereotaxic surgery and microinjection, virus-mediated knockdown of OX2R and pharmacological method, we found that: (1) Intraperitoneal injection of OX2R antagonist Seltorexant induced increased baseline anxiety-like behaviors in male mice. (2) Intraperitoneal injection of OX2R agonist YNT-185 reduced baseline anxiety-like behaviors in male mice. (3) Intraperitoneal injection of YNT-185 alleviated morphine withdrawal-induced anxiety-like behaviors in male mice. (4) Microinjection of YNT-185 into the VTA played anxiolytic effect in male mice. (5) Virus-mediated OX2R knockdown in the VTA induced anxiety-like behaviors in male mice.

01 Sep 2023·European Journal of Pharmacology

Face validation and pharmacologic analysis of Sik3 mutant mouse as a possible model of idiopathic hypersomnia

Article

Author: Yanagisawa, Masashi ; Saitoh, Tsuyoshi ; Suzuki-Abe, Haruka ; Kaushik, Mahesh K ; Funato, Hiromasa ; Ishikawa, Yukiko ; Miyoshi, Chika ; Elhosainy, Asmaa ; Hotta-Hirashima, Noriko ; Kim, Staci J

Idiopathic hypersomnia (IH) is a chronic neurologic disorder with unknown mechanisms that result in long night-time sleep, daytime sleepiness, long non-refreshing naps, and difficult awakening presenting as sleep drunkenness. IH patients are typically diagnosed by shorter sleep latency on multiple sleep latency test (MSLT) along with long sleep time. Only symptomatic drug treatments are currently available for IH and no animal model to study it. Sleepy mice carry a splicing mutation in the Sik3 gene, leading to increased sleep time and sleep need. Here we used a mouse version of MSLT and a decay analysis of wake EEG delta power to validate the Sleepy mutant mouse as an animal model for IH. Sleepy mice had shorter sleep latency in the dark (active) phase than wild-type mice. They also showed lower decay of EEG delta density during wakefulness, possibly reflecting increased sleep inertia. These data indicate that the Sleepy mouse may have partial face validity as a mouse model for idiopathic hypersomnia. We then investigated the effect of orexin-A and the orexin receptor 2-selective agonist YNT-185 on the sleepiness symptoms of the Sleepy mouse. Intracerebroventricular orexin-A promoted wakefulness for 3 h and decreased wake EEG delta density after injection in Sleepy mice and wild-type mice. Moreover, Sleepy mice but not wild-type mice showed a sleep rebound after the orexin-A-induced wakefulness. Intraperitoneal YNT-185 promoted wakefulness for 3 h after injection in Sleepy mice, indicating the potential of using orexin agonists to treat not only orexin deficiency but hypersomnolence of various etiologies.

01 Oct 2020·Bioorganic ChemistryQ2 · CHEMISTRY

From orexin receptor agonist YNT-185 to novel antagonists with drug-like properties for the treatment of insomnia

Q2 · CHEMISTRY

Article

Author: Prchal, Lukas ; Janockova, Jana ; Dolezal, Rafael ; Soukup, Ondrej ; Kobrlova, Tereza ; Korabecny, Jan ; Konecny, Jan ; Mezeiova, Eva ; Karasova-Zdarova, Jana ; Benkova, Marketa

YNT-185 is the first known small molecule acting as orexin 2 receptor (OX₂R) agonist with implication to narcolepsy treatment, served as a template scaffold in generating a small set of seven compounds with predictive affinity to OX₂R. The design of the new small molecules was driven mostly by improving physicochemical properties of the parent drug YNT-185 in parallel with in silico studies, later suggesting their favorable binding modes within the active site of OX₂R. We obtained seven new potential OX₂R binders that were evaluated in vitro for their CNS availability, cytotoxicity, and behavior pattern on OX₂R. Out of them, 15 emerged as the most potent modulator of OX₂R, which, contrary to YNT-185, displayed inverse mode of action, i.e. antagonist profile. 15 was also submitted to an in vivo experiment revealing its ability to permeate through BBB into the brain with a short half-life.

100 Deals associated with YNT-185

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cataplexy	Preclinical	Japan	University of Tsukuba	-
Movement Disorders	Preclinical	Japan	University of Tsukuba	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

YNT-185

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation