Delving into the Latest Updates on S-ethylisothiouronium diethylphosphate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [6]

Target

NOS

Mechanism

NOS inhibitors(Nitric oxide synthase inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesOther Diseases

Active Indication

Cluster HeadacheHypotensionMigraine Disorders

Inactive Indication

Dialysis hypotensionKidney Failure, Chronic

Originator Organization

Meditor Pharmaceuticals Ltd.

Active Organization-

Inactive Organization

Meditor Pharmaceuticals Ltd.

Drug Highest PhaseApproved

First Approval Date

(01 Jan 1997),

Cluster HeadacheHypotensionMigraine Disorders

Regulation-

Login to view timeline

Structure

Molecular FormulaC7H19N2O4PS

InChIKeyCSYSULGPHGCBQD-UHFFFAOYSA-N

CAS Registry21704-46-1

G-quadruplexes (G4s) are DNA or RNA structures formed by guanine-rich repeating sequences. Recently, G4s have become a highly attractive therapeutic target for BRCA-deficient cancers. Here, we show that a substituted quinolone amide compound, MTR-106, stabilizes DNA G-quadruplexes in vitro. MTR-106 displayed significant antiproliferative activity in homologous recombination repair (HR)-deficient and PARP inhibitor (PARPi)-resistant cancer cells. Moreover, MTR-106 increased DNA damage and promoted cell cycle arrest and apoptosis to inhibit cell growth. Importantly, its oral and i.v. administration significantly impaired tumor growth in BRCA-deficient xenograft mouse models. However, MTR-106 showed modest activity against talazoparib-resistant xenograft models. In rats, the drug rapidly distributes to tissues within 5 min, and its average concentrations were 12-fold higher in the tissues than in the plasma. Overall, we identified MTR-106 as a novel G-quadruplex stabilizer with high tissue distribution, and it may serve as a potential anticancer agent.

01 Jan 2008·CardiologyQ4 · MEDICINE

Nitric Oxide Synthase Inhibitor (MTR-105) during Open-Heart Surgery

Q4 · MEDICINE

Article

Author: Borer, Jeffrey S. ; Manolache, Gheorghe ; Ciubotaru, Anatol ; Schachner, Arie ; Ureche, Andrei ; Sasson, Lior

Objectives: Hypotension is common immediately following cardiopulmonary bypass. Experimentally, MTR-105 (S-ethylisothiuronium diethylphosphate), a fast-acting synthetic nitric oxide synthase inhibitor, rapidly increases blood pressure. The purpose of the current study was to assess the influence of MTR-105 on hemodynamics early after cardiopulmonary bypass in patients undergoing open-heart surgery. Methods:Thirty-six patients with an ejection fraction >50% undergoing open-heart surgery were randomly assigned to either 50 µg kg–1 min–1 MTR-105 (M50, n = 12), 10 µg kg–1 min–1 MTR-105 (M10, n = 12) or buffered phosphate solution (placebo control, n = 12). Half suffered from atrial fibrillation and 75% had severe tricuspid regurgitation. Patients received the drug for 6 h after cross-clamp removal. Hemodynamic variables were measured before drug administration until 24 h after operation. Adverse events were recorded from study drug initiation through 30 days after the operation. Results:Compared with control, both MTR-105 doses were associated with an immediate increase in systemic blood pressure (16%) and systemic vascular resistance and a decrease in cardiac index. Half-life time of MTR-105 was calculated to be 4.1 ± 0.8 h (M10) and 4.45 ± 0.92 h (M50). Three patients died during hospitalization, unrelated to the study medication. Conclusions:At the doses employed, MTR-105 appears hemodynamically active in increasing both blood pressures.

Radiatsionnaia biologiia, radioecologiia

[The estimation of the nitric oxide role in the aggravation of combined radiation-thermal injuries].

Article

Author: Budagov, R S ; Skvotsov, V G ; Ul'ianova, L P ; Proskuriakov, S Ia

The influence of specific inhibitor of inducible NO synthase S-ethil-isothiourea (as "Difetur" preparation) on liver NO production level, and 30-days survival, mean survival time and probability of mortality within animals under combined radiation/thermal injury (CRTI) were evaluated. Experiments were carrying out on mice (whole body gamma-irradiation at the dose of 7 Gy + 10% body surface full-thickness thermal burn). It was shown, that CRTI induce 2-fold statistical significant increase of NO production in liver of experimental animals. Mice pretreatment with Difetur preparation lead to practically full inhibition of NO production. In the group of animals, with Difetur administration during first two days after CRTI 60% mice survived as compared 15% survive in control group. In pair with data on probability of mortality it was suggested that growth of NO production in the early period of CRTI increase sensitivity of animals to pathological processes leading to death on 10-12 days.

100 Deals associated with S-ethylisothiouronium diethylphosphate

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	S-ethylisothiouronium diethylphosphate	C	-

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Cluster Headache	-	-	01 Jan 1997
Hypotension	-	-	01 Jan 1997
Migraine Disorders	-	-	01 Jan 1997

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Kidney Failure, Chronic	Phase 2	IL	Meditor Pharmaceuticals Ltd.	01 May 2006
Hypotension	Phase 1	US	Meditor Pharmaceuticals Ltd.	01 Jan 2008
Dialysis hypotension	Preclinical	IL	Meditor Pharmaceuticals Ltd.	01 May 2006