Kv7.2 agonists(Voltage-gated potassium channel subunit Kv7.2 agonists), Kv7.3 stimulants(Potassium voltage-gated channel subfamily KQT member 3 stimulants), Kv7.4 stimulators(potassium voltage-gated channel subfamily Q member 4 stimulants)

Therapeutic Areas

Nervous System Diseases

Active Indication

Epilepsy

Inactive Indication-

Originator Organization

Hebei Medical University

Active Organization

SSY Group Ltd.

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC18H8Cl2F4N4O

InChIKeyJEXACLGXUUYXDX-UHFFFAOYSA-N

CAS Registry1259536-62-3

100 Clinical Results associated with QO-58

100 Translational Medicine associated with QO-58

100 Patents (Medical) associated with QO-58

Literatures (Medical) associated with QO-58

05 Feb 2025·Biological and Pharmaceutical Bulletin

Potentiation of Nicotine-Induced Currents by QO58, a Kv7 Channel Opener, in Intracardiac Ganglion Neurons of Rats

Article

Author: Ogata, Masanori ; Ishibashi, Hitoshi ; Sasaki-Hamada, Sachie ; Arichi, Shiho ; Eto, Kei

QO58 (5-(2,6-dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)-1H-[1,5-a] pyrimidin-7-one) is currently used as a specific activator of the Kv7 (KCNQ) family of K⁺ channels. Here, we report an unexpected potentiating effect of this drug on nicotinic acetylcholine receptors. We recorded the whole-cell responses to the rapid application of nicotine with the Cs⁺-based pipette solution in intracardiac ganglion neurons freshly dissociated from the rat heart. Nicotine-induced inward currents were concentration-dependently blocked by mecamylamine, but not by 1 μM atropine at a holding potential of -60 mV. While the application of QO58 per se evoked a persistent inward current at this holding potential, 10 μM QO58 potentiated the peak amplitude of the nicotine-induced current. The QO58-induced inward currents were inhibited by the Kv7 channel blockers XE991 and Ba²⁺, but not by mecamylamine. On the other hand, the nicotine-induced current potentiated by QO58 was fully inhibited by mecamylamine. The facilitatory action of QO58 on the nicotinic response was unaffected by Ba²⁺. QO58 did not affect the reversal potential of the nicotine-induced current. QO58 apparently shifted the concentration-response curve of nicotine to the left. The half-maximal effective concentrations for nicotine in the absence and presence of 10 μM QO58 were 10.2 and 4.3 μM, respectively. These results suggest that QO58 acts as a positive allosteric modulator of nicotinic acetylcholine receptors. Given the prevalence of nicotinic receptor signaling, the present observations should be considered in future studies on the roles of Kv7 channels in the function of neural circuits and diseases.

01 Feb 2023·Biophysical Journal

Voltage sensor targeted activation of Kv7 channels by QO-58

Article

Author: Kanyo, Richard

29 Jan 2022·Cardiovascular ResearchQ1 · MEDICINE

Impaired Kv7 channel activity in the central amygdala contributes to elevated sympathetic outflow in hypertension

Q1 · MEDICINE

Article

Author: Gu, Zezong ; Sheng, Zhao-Fu ; Phaup, Jeffery G ; Chen, Shanyan ; Yeh, Edward T H ; Zheng, PeiRu ; Pan, Hui-Lin ; Li, De-Pei ; Chang, Hui-Ming ; Zhang, Hua ; Zhou, Jing-Jing

AbstractAimsElevated sympathetic outflow is associated with primary hypertension. However, the mechanisms involved in heightened sympathetic outflow in hypertension are unclear. The central amygdala (CeA) regulates autonomic components of emotions through projections to the brainstem. The neuronal Kv7 channel is a non-inactivating voltage-dependent K+ channel encoded by KCNQ2/3 genes involved in stabilizing the neuronal membrane potential and regulating neuronal excitability. In this study, we investigated if altered Kv7 channel activity in the CeA contributes to heightened sympathetic outflow in hypertension.Methods and resultsThe mRNA and protein expression levels of Kv7.2/Kv7.3 in the CeA were significantly reduced in spontaneously hypertensive rats (SHRs) compared with Wistar–Kyoto (WKY) rats. Lowering blood pressure with coeliac ganglionectomy in SHRs did not alter Kv7.2 and Kv7.3 channel expression levels in the CeA. Fluospheres were injected into the rostral ventrolateral medulla (RVLM) to retrogradely label CeA neurons projecting to the RVLM (CeA–RVLM neurons). Kv7 channel currents recorded from CeA–RVLM neurons in brain slices were much smaller in SHRs than in WKY rats. Furthermore, the basal firing activity of CeA–RVLM neurons was significantly greater in SHRs than in WKY rats. Bath application of specific Kv7 channel blocker 10, 10-bis (4-pyridinylmethyl)-9(10H)-anthracnose (XE-991) increased the excitability of CeA–RVLM neurons in WKY rats, but not in SHRs. Microinjection of XE-991 into the CeA increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA), while microinjection of Kv7 channel opener QO-58 decreased ABP and RSNA, in anaesthetized WKY rats but not SHRs.ConclusionsOur findings suggest that diminished Kv7 channel activity in the CeA contributes to elevated sympathetic outflow in primary hypertension. This novel information provides new mechanistic insight into the pathogenesis of neurogenic hypertension.

100 Deals associated with QO-58

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Epilepsy	Preclinical	China	SSY Group Ltd.	-

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

QO-58

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation