Delving into the Latest Updates on Y-3 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Y3

+ [6]

Target

GABAA receptor x PSD95 x nNOS

Mechanism

GABAA receptor agonists(Gamma-aminobutyric acid A receptor agonists), PSD95 inhibitors(Disks large homolog 4 inhibitors), nNOS inhibitors(Nitric-oxide synthase, brain inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular Diseases

Active Indication

Acute Ischemic Stroke

Inactive Indication-

Originator Organization

Nanjing Ningdan New Drug Technology Co., Ltd.

Active Organization

Nanjing Ningdan New Drug Technology Co., Ltd.

China Medical System Holdings Ltd.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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BackgroundPoststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke. ZL006-05, a dual-target analgesic we developed, dissociates nitric oxide synthase from postsynaptic density-95 while potentiates α2-containing γ-aminobutyric acid type A receptor. This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects.MethodsPhotothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice. Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride) staining or Nissl staining. Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores. Grid-walking, cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions. Spatial learning was assessed using Morris water maze task. Depression and anxiety were induced by unpredictable chronic mild stress. Depressive behaviours were assessed by tail suspension, forced swim and sucrose preference tests. Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests. Pharmacokinetics, toxicokinetics and long-term toxicity studies were performed in rats.ResultsAdministration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly, with a treatment window of 12 hours after ischemia, and reduced plasminogen activato-induced haemorrhagic transformation. ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice, had antidepressant and anxiolytic effects in stroke mice. ZL006-05 crossed the blood–brain barrier and distributed into the brain rapidly, and had a high safety profile in toxicokinetics and long-term toxicological studies.ConclusionZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy, safety and targeting of clinical issues.

01 Sep 2023·Neuropharmacology

Trimethoxyflavanone relieves Paclitaxel-induced neuropathic pain via inhibiting expression and activation of P2X7 and production of CGRP in mice

Article

Author: Xu, Yuhao ; Gao, Yinping ; Lin, Pengyu ; Miao, Mengmeng ; Pan, Chen ; Mei, Changqing ; Wu, Wenwei ; Lu, Qichen ; Chen, Xiaowei ; Ni, Feng ; Xu, Linbin ; Yu, Yang ; Xu, Jia

Paclitaxel (PTX) is an anticancer drug used to treat solid tumors, but one of its common adverse effects is chemotherapy-induced peripheral neuropathy (CIPN). Currently, there is limited understanding of neuropathic pain associated with CIPN and effective treatment strategies are inadequate. Previous studies report the analgesic actions of Naringenin, a dihydroflavonoid compound, in pain. Here we observed that the anti-nociceptive action of a Naringenin derivative, Trimethoxyflavanone (Y3), was superior to Naringenin in PTX-induced pain (PIP). An intrathecal injection of Y3 (1 μg) reversed the mechanical and thermal thresholds of PIP and suppressed the PTX-induced hyper-excitability of dorsal root ganglion (DRG) neurons. PTX enhanced the expression of ionotropic purinergic receptor P2X7 (P2X7) in satellite glial cells (SGCs) and neurons in DRGs. The molecular docking simulation predicts possible interactions between Y3 and P2X7. Y3 reduced the PTX-enhanced P2X7 expression in DRGs. Electrophysiological recordings revealed that Y3 directly inhibited P2X7-mediated currents in DRG neurons of PTX-treated mice, suggesting that Y3 suppressed both expression and function of P2X7 in DRGs post-PTX administration. Y3 also reduced the production of calcitonin gene-related peptide (CGRP) in DRGs and at the spinal dorsal horn. Additionally, Y3 suppressed the PTX-enhanced infiltration of Iba1-positive macrophage-like cells in DRGs and overactivation of spinal astrocytes and microglia. Therefore, our results indicate that Y3 attenuates PIP via inhibiting P2X7 function, CGRP production, DRG neuron sensitization, and abnormal spinal glial activation. Our study implies that Y3 could be a promising drug candidate against CIPN-associated pain and neurotoxicity.

02 Aug 2023·Foods (Basel, Switzerland)

Isolation of Aroma-Producing Wickerhamomyces anomalus Yeast and Analysis of Its Typical Flavoring Metabolites.

Article

Author: Yin, Liguo ; Liu, Hongyu ; Zhou, Jing ; Zhang, Jing ; Yang, Jiao ; Hu, Rong ; Zhao, Xingxiu ; He, Yiguo ; Cheng, Tao

In this study, 21 strains of aroma-producing yeast were isolated from Sichuan paocai juice of farmers in western, eastern and southern Sichuan. One strain, Y3, with the best aroma-producing characteristics, was screened using an olfactory method and a total ester titration method, and was identified as Wickerhamomyces anomalus. The total ester content of Y3 fermentation broth was as high as 1.22 g/L, and there was no white colonies or film on the surface. Meanwhile, the Y3 strain could tolerate 14% salt concentration conditions and grow well in a pH range of 3-4. Through sensory analysis, the fermented mustard with a ratio of Lactiplantibacillus plantarum to Y3 of 1:1 showed the highest overall acceptability. Ethyl acetate with its fruit and wine flavor was also detected in the fermented Sichuan paocai juice with a mixed bacteria ratio of 1:1, analyzed with SPME-GC-MS technology, as well as phenylethyl alcohol, isobutyl alcohol, isothiocyanate eaters, myrcene and dimethyl disulfide. These contributed greatly to the unique flavor of Sichuan paocai. In general, Wickerhamomyces anomalus Y3 enhanced the aroma of the fermented Sichuan paocai.

100 Deals associated with Y-3

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	Phase 3	CN	China Medical System Holdings Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2023	Not Applicable	Acute Myeloid Leukemia	112	Azacitidine-Venetoclax-Chidamide (ABC) regimen	kfoozfrtvq(oxosvkcnlj) = axwgqmlghq tqtejhdtoq (ggmpdzwwvi ) View more	-	09 Dec 2023
				"3+7" regimen	kfoozfrtvq(oxosvkcnlj) = hyuuskbfbj tqtejhdtoq (ggmpdzwwvi ) View more