NecroX-5(NecroX-5) - 药物靶点：RIPK1_在研适应症：肺纤维化_专利_临床

概要

基本信息

药物类型

小分子化药

别名

NX-5、NECROX-5

靶点

RIPK1

作用机制

RIPK1抑制剂(受体相互作用的丝氨酸/苏氨酸蛋白激酶-1抑制剂)

治疗领域

呼吸系统疾病

在研适应症

肺纤维化

非在研适应症-

原研机构

Jeonbuk National University Hospital

在研机构

Jeonbuk National University Hospital

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-

关联

100 项与 NecroX-5 相关的临床结果

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100 项与 NecroX-5 相关的转化医学

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100 项与 NecroX-5 相关的专利（医药）

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54

项与 NecroX-5 相关的文献（医药）

2023-07-01·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

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

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.

2023-06-01·Pharmacological reports : PR

CYX-5, a G-protein biassed MOP receptor agonist, DOP receptor antagonist and KOP receptor agonist, evokes constipation but not respiratory depression relative to morphine in rats

Article

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

Abstract:

Background:

Strong opioid analgesics such as morphine alleviate moderate to severe acute nociceptive pain (e.g. post-surgical or post-trauma pain) as well as chronic cancer pain. However, they evoke many adverse effects and so there is an unmet need for opioid analgesics with improved tolerability. Recently, a prominent hypothesis has been that opioid-related adverse effects are mediated by β-arrestin2 recruitment at the µ-opioid (MOP) receptor and this stimulated research on discovery of G-protein biassed opioid analgesics. In other efforts, opioids with MOP agonist and δ-opioid (DOP) receptor antagonist profiles are promising for reducing side effects c.f. morphine. Herein, we report on the in vivo pharmacology of a novel opioid peptide (CYX-5) that is a G-protein biassed MOP receptor agonist, DOP receptor antagonist and kappa opioid (KOP) receptor agonist.

Methods:

Male Sprague–Dawley received intracerebroventricular bolus doses of CYX-5 (3, 10, 20 nmol), morphine (100 nmol) or vehicle, and antinociception (tail flick) was assessed relative to constipation (charcoal meal and castor oil-induced diarrhoea tests) and respiratory depression (whole body plethysmography).

Results:

CYX-5 evoked naloxone-sensitive, moderate antinociception, at the highest dose tested. Although CYX-5 did not inhibit gastrointestinal motility, it reduced stool output markedly in the castor oil-induced diarrhoea test. In contrast to morphine that evoked respiratory depression, CYX-5 increased tidal volume, thereby stimulating respiration.

Conclusion:

Despite its lack of recruitment of β-arrestin2 at MOP, DOP and KOP receptors, CYX-5 evoked constipation, implicating a mechanism other than β-arrestin2 recruitment at MOP, DOP and KOP receptors, mediating constipation evoked by CYX-5 and potentially other opioid ligands.

2022-12-01·RESPIRATORY RESEARCH2区 · 医学

NecroX-5 ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3-mediated epithelial–mesenchymal transition

2区 · 医学

ArticleOA

作者: Feng, Yuan ; Dan, Feng ; Sheng-Xiong, Tong ; Shao-Jun, Li ; Jia-Yu, Tian ; Min, Li ; Shu-Li, Zhang ; Xiang-Zhi, Fang ; Han, Hu

Abstract:

Background:

Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis.

Results:

We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial–mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-β1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM.

Conclusions:

Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.

100 项与 NecroX-5 相关的药物交易

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