δ opioid receptor antagonists(δ-opioid receptor antagonists), κ opioid receptor antagonists(Kappa opioid receptor antagonists), μ opioid receptor agonists(Mu opioid receptor agonists)

Therapeutic Areas

Nervous System Diseases

Active Indication

Analgesia

Inactive Indication-

Originator Organization

Nanjing Medical University

Active Organization

Nanjing Medical University

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with CYX-6

100 Translational Medicine associated with CYX-6

100 Patents (Medical) associated with CYX-6

Literatures (Medical) associated with CYX-6

01 Jul 2023·European journal of drug metabolism and pharmacokinetics

In Vitro Assessment of the Metabolic Stability of Two Novel Endomorphin-2 Analogs, CYX-5 and CYX-6, in Rat Liver Microsomes.

Letter

Author: Cai, Yunxin ; Ghassabian, Sussan ; Li, Tingyou ; Kuo, Andy ; Imam, Mohammad Zafar ; Smith, Maree T. ; Qin, Yajuan

This study is on the in vitro assessment of the metabolic stability of two novel endomorphin-2 analogs, CYX-5 and CYX-6, in rat liver microsomes.We have recently reported two G-protein-biased endomorphin-2 (EM-2; H-Tyr-Pro-Phe-Phe-NH2) analogs, namely CYX-6 (H-Dmt-Pro-Tmp-Tmp-NH2) and CYX-5 (H-Dmt-Pro-1-Nal-NH2), which showed improved opioid-related adverse-effect profiles in rats relative to morphine.CYX-6 and CYX-5 given by bolus intracerebroventricular administration in rats had superior constipation and respiratory profiles compared with the pos. control morphine.Hence, we designed this study to gain insight into the metabolic stability of these compounds before progressing to a systemic dosing route.Specifically, our aim was to assess the in vitro metabolic stability of CYX-6 and CYX-5 in rat liver microsomes (Sigma Aldrich Pty Ltd, Castle Hill, NSW, Australia) according to the methods described by Pippin et al.The good metabolic stability of the CYX compounds herein affirms their satisfactory stability at supraspinal and spinal sites in the central nervous system after intracerebroventricular administration in rats.The relatively long in vitro half-life of CYX-6 in rat liver microsomes (2.2 h) suggests that it may have a favorable pharmacokinetic profile after systemic administration in rats.

01 Mar 2020·European Journal of PharmacologyQ3 · MEDICINE

Intracerebroventricular administration of CYX-6, a potent μ-opioid receptor agonist, a δ- and κ-opioid receptor antagonist and a biased ligand at μ, δ & κ-opioid receptors, evokes antinociception with minimal constipation and respiratory depression in rats in contrast to morphine

Q3 · MEDICINE

Article

Author: Li, Tingyou ; Qin, Yajuan ; Kuo, Andy ; Cai, Yunxin ; Smith, Maree T ; Ghassabian, Sussan ; Imam, Mohammad Zafar

Mu opioid receptor (MOPr) agonists are thought to produce analgesia via modulation of G-protein-coupled intracellular signalling pathways whereas the β-arrestin2 pathway is proposed to mediate opioid-related adverse effects. Here, we report the antinociception, constipation and respiratory depressant profile of CYX-6, a potent MOPr agonist that is also a delta and a kappa opioid receptor (DOPr/KOPr) antagonist and that lacks β-arrestin2 recruitment at each of the MOPr, DOPr and the KOPr. In anaesthetised male Sprague Dawley rats, an intracerebroventricular (i.c.v.) guide cannula was stereotaxically implanted. After 5-7 days post-surgical recovery, rats received a single i.c.v. bolus dose of CYX-6 (3-30 nmol), morphine (100 nmol) or vehicle. Antinociception was assessed using the warm water tail flick test (52.5 ± 0.5 °C). Constipation was assessed using the charcoal meal gut motility test and the castor oil-induced diarrhoea test. Respiratory depression was measured by whole-body plethysmography in awake, freely moving animals, upon exposure to a hypercapnic gas mixture (8% CO₂, 21% O₂ and 71% N₂). The intrinsic pharmacology of CYX-6 given by the i.c.v. route in rats showed that it produced dose-dependent antinociception. It also produced respiratory stimulation rather than depression and it had a minimal effect on intestinal motility in contrast to the positive control, morphine. CYX-6 is an endomorphin-2 analogue that dissociates antinociception from constipation and respiratory depression in rats. Our findings provide useful insight to inform the discovery and development of novel opioid analgesics with a superior tolerability profile compared with morphine.

01 Apr 2014·Bioorganic & Medicinal ChemistryQ3 · MEDICINE

Endomorphin analogues with mixed μ-opioid (MOP) receptor agonism/δ-opioid (DOP) receptor antagonism and lacking β-arrestin2 recruitment activity

Q3 · MEDICINE

Article

Author: Li, Tingyou ; Cai, Jun ; Lam, Ai-Leen ; Ma, Yu ; Ambo, Akihiro ; Magiera, Julia ; Cai, Yunxin ; Song, Bowen ; Smith, Maree T ; Lazarus, Lawrence H ; Sasaki, Yusuke ; Sekar, Sunder ; Wyse, Bruce D

Analogues of endomorphin (Dmt-Pro-Xaa-Xaa-NH2) modified at position 4 or at positions 4 and 3, and tripeptides (Dmt-Pro-Xaa-NH2) modified at position 3, with various phenylalanine analogues (Xaa=Trp, 1-Nal, 2-Nal, Tmp, Dmp, Dmt) were synthesized and their effects on in vitro opioid activity were investigated. Most of the peptides exhibited high μ-opioid (MOP) receptor binding affinity (KiMOP=0.13-0.81nM), modest MOP-selectivity (Kiδ-opioid (DOP)/KiMOP=3.5-316), and potent functional MOP agonism (GPI, IC50=0.274-249nM) without DOP and κ-opioid (KOP) receptor agonism. Among them, compounds 7 (Dmt-Pro-Tmp-Tmp-NH2) and 9 (Dmt-Pro-1-Nal-NH2) were opioids with potent mixed MOP receptor agonism/DOP receptor antagonism and devoid of β-arrestin2 recruitment activity. They may offer a unique template for the discovery of potent analgesics that produce less respiratory depression, less gastrointestinal dysfunction and that have a lower propensity to induce tolerance and dependence compared with morphine.

100 Deals associated with CYX-6

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Analgesia	Preclinical	China	Nanjing Medical University	24 Feb 2014

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

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

view full example data

Regulation

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

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

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

CYX-6

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation