更新于：2024-11-21

NS-102

更新于：2024-11-21

概要

研发状态

概要

基本信息

药物类型

小分子化药

别名

靶点

AMPA receptor x Kainate受体

作用机制

AMPA receptor拮抗剂(离子型谷氨酸受体AMPA拮抗剂)、Kainate受体拮抗剂

治疗领域-

在研适应症-

非在研适应症-

原研机构

NTG Nordic Transport Group A/S

在研机构

NTG Nordic Transport Group A/S

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C12H11N3O4

InChIKeySCDBMLHUXJBJSS-UHFFFAOYSA-N

CAS号136623-01-3

关联

100 项与 NS-102 相关的临床结果

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100 项与 NS-102 相关的转化医学

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100 项与 NS-102 相关的专利（医药）

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项与 NS-102 相关的文献（医药）

2023-10-01·Protein & Peptide Letters

Activation and Denitrosylation of Procaspase-3 in KA-induced Excitotoxicity

Article

作者: Zhang, Jia ; Liu, Yong ; Lu, Feng ; Liu, Ying-Kui ; Yin, Xiao-Hui ; Yan, Hui ; Cai, Yu-Ting ; Li, Chong

Background:It has been reported that activation of glutamate kainate receptor subunit 2 (GluK2) subunit-containing glutamate receptors and the following Fas ligand(FasL) up-regulation, caspase-3 activation, result in delayed apoptosis-like neuronal death in hippocampus CA1 subfield after cerebral ischemia and reperfusion. Nitric oxide-mediated S-nitrosylation might inhibit the procaspase activation, whereas denitrosylation might contribute to cleavage and activation of procaspases.Objectives:The study aimed to elucidate the molecular mechanisms underlying procaspase-3 denitrosylation and activation following kainic acid (KA)-induced excitotoxicity in rat hippocampus.Methods:S-nitrosylation of procaspase-3 was detected by biotin-switch method. Activation of procaspase-3 was shown as cleavage of procaspase-3 detected by immunoblotting. FasL expression was detected by immunoblotting. Cresyl violets and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining were used to detect apoptosis-like neuronal death in rat hippocampal CA1 and CA3 subfields.Results:KA led to the activation of procaspase-3 in a dose- and time-dependent manner, and the activation was inhibited by KA receptor antagonist NS102. Procaspase-3 was denitrosylated at 3 h after kainic acid administration, and the denitrosylation was reversed by SNP and GSNO. FasL ASODNs inhibited the procaspase-3 denitrosylation and activation. Moreover, thioredoxin reductase (TrxR) inhibitor auranofin prevented the denitrosylation and activation of procaspase-3 in rat hippocampal CA1 and CA3 subfields. NS102, FasL AS-ODNs, and auranofin reversed the KAinduced apoptosis and cell death in hippocampal CA1 and CA3 subfields.Conclusions:KA led to denitrosylation and activation of procaspase-3 via FasL and TrxR. Inhibition of procaspase-3 denitrosylation by auranofin, SNP, and GSNO played protective effects against KA-induced apoptosis-like neuronal death in rat hippocampal CA1 and CA3 subfields. These investigations revealed that the procaspase-3 undergoes an initial denitrosylation process before becoming activated, providing valuable insights into the underlying mechanisms and possible treatment of excitotoxicity.

2020-03-01·The Oncologist2区 · 医学

Bevacizumab in Combination with TAS-102 Improves Clinical Outcomes in Patients with Refractory Metastatic Colorectal Cancer: A Retrospective Study

2区 · 医学

Article

作者: Hirose, Chiemi ; Ishihara, Takuma ; Kitahora, Mika ; Fujii, Hironori ; Matsuhashi, Nobuhisa ; Watanabe, Daichi ; Suzuki, Akio ; Takahashi, Takao ; Yamada, Yunami ; Yoshida, Kazuhiro ; Iihara, Hirotoshi

AbstractObjectiveTAS-102 is effective for treating patients with metastatic colorectal cancer (mCRC). This study determined whether combining bevacizumab (Bmab) with TAS-102 improves clinical outcomes in refractory mCRC.Patients and MethodsWe retrospectively analyzed data from Japanese patients with refractory mCRC who received TAS-102 (35 mg/m2, twice a day) with (T-B group) or without Bmab (TAS-102 monotherapy; T group) between July 2014 and December 2018. The primary endpoint was median overall survival (OS), and secondary endpoints were median time to treatment failure, overall response rate, and the incidence of adverse events. Clinical outcomes were compared using propensity score matched analysis.ResultsData from 57 patients were analyzed (T-B group: 21 patients, T group: 36 patients). Median OS was significantly longer in the T-B group than the T group (14.4 months vs. 4.5 months, p < .001). Cox proportional hazard analysis showed that combination therapy with Bmab was significantly correlated with OS. Propensity score matched analysis confirmed that the median OS was significantly longer in the T-B group than the T group (14.4 months vs. 6.1 months, p = .006) and that there was a significant correlation between Bmab and OS. The incidence of hypertension (grade ≥2) as an adverse event was significantly higher in the T-B group than the T group (23.8% vs. 0.0%, p = .005), whereas other adverse events were comparable between the two groups.ConclusionTreatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC refractory to standard therapies.

2017-11-01·British Journal of Anaesthesia1区 · 医学

Sevoflurane activates hippocampal CA3 kainate receptors (Gluk2) to induce hyperactivity during induction and recovery in a mouse model

1区 · 医学

Article

作者: Huang, H ; Zhou, C ; Liao, D ; Li, F ; Liang, P ; Liu, J

BACKGROUNDIn addition to general anaesthetic effects, sevoflurane can also induce hyperactive behaviours during induction and recovery, which may contribute to neurotoxicity; however, the mechanism of such effects is unclear. Volatile anaesthetics including isoflurane have been found to activate the kainate (GluK2) receptor. We developed a novel mouse model and further explored the involvement of kainate (GluK2) receptors in sevoflurane-induced hyperactivity.METHODSMaximal speed, mean speed, total movement distance and resting percentage of C57BL/6 mice were quantitatively measured using behavioural tracking software before and after sevoflurane anaesthesia. Age dependence of this model was also analysed and sevoflurane-induced hyperactivity was evaluated after intracerebral injection of the GluK2 receptor blocker NS-102. Neurones from the hippocampal CA3 region were used to undertake in vitro electrophysiological measurement of kainate currents and miniature excitatory postsynaptic potential (mEPSP).RESULTSSevoflurane induced significant hyperactivities in mice under sevoflurane 1% anaesthesia and during the recovery period, characterized as increased movement speed and total distance. The hyperactivity was significantly increased in young mice compared with adults (P<0.01) and pre-injection of NS-102 significantly prevented this sevoflurane-induced hyperactivity. In electrophysiological experiments, sevoflurane significantly increased the frequency of mEPSP at low concentrations and evoked kainate currents at high concentrations.CONCLUSIONSWe developed a behavioural model in mice that enabled characterization of sevoflurane-induced hyperactivity. The kainate (GluK2) receptor antagonist attenuated these sevoflurane-induced hyperactivities in vivo, suggesting that kainate receptors might be the underlying therapeutic targets for sevoflurane-induced hyperactivities in general anaesthesia.

100 项与 NS-102 相关的药物交易

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