Last update 21 Nov 2024

Linsidomine Hydrochloride

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Linsidomine, Corvasal

Target-

Mechanism-

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Hypertension

Inactive Indication-

Originator Organization-

Active Organization-

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

Structure

Molecular FormulaC6H11ClN4O2

InChIKeyZRFWHHCXSSACAW-UHFFFAOYSA-M

CAS Registry16142-27-1

View All Structures (2)

100 Clinical Results associated with Linsidomine Hydrochloride

100 Translational Medicine associated with Linsidomine Hydrochloride

100 Patents (Medical) associated with Linsidomine Hydrochloride

1,035

Literatures (Medical) associated with Linsidomine Hydrochloride

01 Oct 2024·Biochemistry

Inhibition of Sirtuin Deacylase Activity by Peroxynitrite

Article

Author: Wynia-Smith, Sarah L. ; Jones Lipinski, Rachel A. ; Bohl, Kelsey ; Smith, Brian C.

Sirtuins are a class of enzymes that deacylate protein lysine residues using NAD⁺ as a cosubstrate. Sirtuin deacylase activity has been historically regarded as protective; loss of sirtuin deacylase activity potentially increases susceptibility to aging-related disease development. However, which factors may inhibit sirtuins during aging or disease is largely unknown. Increased oxidant and inflammatory byproduct production damages cellular proteins. Previously, we and others found that sirtuin deacylase activity is inhibited by the nitric oxide (NO)-derived cysteine post-translational modification S-nitrosation. However, the comparative ability of the NO-derived oxidant peroxynitrite (ONOO^-) to affect human sirtuin activity had not yet been assessed under uniform conditions. Here, we compare the ability of ONOO^- (donated from SIN-1) to post-translationally modify and inhibit SIRT1, SIRT2, SIRT3, SIRT5, and SIRT6 deacylase activity. In response to SIN-1 treatment, inhibition of SIRT1, SIRT2, SIRT3, SIRT5, and SIRT6 deacylase activity correlated with increased tyrosine nitration. Mass spectrometry identified multiple novel tyrosine nitration sites in SIRT1, SIRT3, SIRT5, and SIRT6. As each sirtuin isoform has at least one tyrosine nitration site within the catalytic core, nitration may result in sirtuin inhibition. ONOO^- can also react with cysteine residues, resulting in sulfenylation; however, only SIRT1 showed detectable peroxynitrite-mediated cysteine sulfenylation. While SIRT2, SIRT3, SIRT5, and SIRT6 showed no detectable sulfenylation, SIRT6 likely undergoes transient sulfenylation, quickly resolving into an intermolecular disulfide bond. These results suggest that the aging-related oxidant peroxynitrite can post-translationally modify and inhibit sirtuins, contributing to susceptibility to aging-related disease.

01 Aug 2024·Physiological Reports

Nitric oxide is involved in the cardioprotection of neonatal rat hearts, but not in neonatal ischemic postconditioning

Article

Author: Minaříková, Marcela ; Doul, Jan ; Maxová, Hana ; Charvátová, Zuzana

AbstractThe cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by nitric oxide (NO). During the early developmental period, rat hearts exhibit higher resistance to ischemia–reperfusion (I/R) injury, contain higher levels of serum nitrates, and their resistance cannot be further increased by IPC or IPoC. NOS blocker (L‐NAME) lowers their high resistance. Wistar rat hearts (postnatal Days 1 and 10) were perfused according to Langendorff and exposed to 40 min of global ischemia followed by reperfusion with or without IPoC. NO and reactive oxygen species donors (DEA‐NONO, SIN‐1) and L‐NAME were administered. Tolerance to ischemia decreased between Days 1 and 10. DEA‐NONO (low concentrations) significantly increased tolerance to I/R injury on both Days 1 and 10. SIN‐1 increased tolerance to I/R injury on Day 10, but not on Day 1. L‐NAME significantly reduced resistance to I/R injury on Day 1, but actually increased resistance to I/R injury on Day 10. Cardioprotection by IPoC on Day 10 was not affected by either NO donors or L‐NAME. It can be concluded that resistance of the neonatal heart to I/R injury is NO dependent, but unlike in adult hearts, cardioprotective interventions, such as IPoC, are most likely NO independent.

18 Feb 2024·International Journal of Ophthalmology

A highly sensitive fluorescent probe RN-NA reveals peroxynitrite as a novel biomarker for primary open angle glaucoma

Article

Author: Lei, Yuan ; Chen, Yu-Hong ; Liu, Ke-Yin ; Zhang, You-Jia ; Bao, Luo ; Qin, Bo

AIM: To directly quantify peroxynitrite (ONOO-) using a highly sensitive fluorescence resonance energy transfer probe RN-NA, investigate the association between ONOO- and primary open angle glaucoma (POAG), and clarify whether RN-NA could be used as a potential tool for POAG diagnosis. METHODS: Plasma and aqueous humor (AH) samples were collected from POAG patients (n=100, age: 59.70±6.87y) and age-related cataract (ARC) patients (n=100, age: 61.15±4.60y) admitted to our hospital. Next, RN-NA was used to detect ONOO- in plasma and AH samples, and the relationship between ONOO- level and POAG was analyzed using binary logistic regression. Besides, Pearson correlation analysis was applied to characterize the correlation of the levels of ONOO- with the patients’ age, intraocular pressure (IOP), and mean deviation of visual field testing. The ONOO- scavenger MnTMPyP was employed to treat the 3-morpholinosyndnomine (SIN-1)-induced ocular hypertension in mice (n=7, 6-8wk). Finally, the IOP and ONOO- in both eyes were measured 30min after the last drug treatment. RESULTS: ONOO- levels of AH and plasma were significantly higher in the POAG group than in the ARC group (P<0.01). Additionally, ONOO- levels were closely correlated with POAG in a binary logistic regression analysis [odds ratio (OR)=1.008, 95% confidence interval (CI): 1.002-1.013, P<0.01 for AH; OR=1.004, 95%CI: 1.002-1.006, P<0.001 for plasma]. Pearson correlation analysis showed that ONOO- levels in AH or plasma were positively associated with visual field defects (R=0.51, P<0.01 for AH; R=0.45, P<0.001 for plasma), and ONOO- levels in plasma and AH were correlated in the POAG group (R=0.69, P<0.001). However, administering MnTMPyP to mouse eyes reversed the elevated IOP caused by SIN-1 (P<0.05). CONCLUSION: ONOO- levels in AH and plasma, detected by RN-NA, are significantly related to POAG and positively correlated with visual field defects in POAG patients. Hence, ONOO- is a potential biomarker of POAG, especially advanced POAG. Besides, anti-nitration compounds may be novel ocular hypotensive agents based on the animal study.

100 Deals associated with Linsidomine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
-	Linsidomine Hydrochloride	C01DX18	DB13400

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Hypertension	-	-	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EULAR2015	Not Applicable	Muscular Atrophy	-	L-NAME	iwqduuxhwq(hslmdfweid) = mghddndszi vshhbhbsld (ctqzhjpvth, 121) View more	-	10 Jun 2015
				SIN-1	iwqduuxhwq(hslmdfweid) = sorfyqelfp vshhbhbsld (ctqzhjpvth, 169) View more

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

Linsidomine Hydrochloride

Overview

Basic Info

Structure

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation