氟莱哌素(Fluorapacin) - 药物靶点：Tubulin_在研适应症：肺癌，非小细胞肺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

BFBTS、FLP

靶点

Tubulin

作用机制

微管蛋白抑制剂

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

ACEA Therapeutics, Inc.初创企业

非在研机构

安捷伦生物（杭州）有限公司

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)临床2期

特殊审评-

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结构/序列

分子式C14H12F2S3

InChIKeyXCOWUOOCXCXCNS-UHFFFAOYSA-N

CAS号869811-23-4

关联

3

项与氟莱哌素相关的临床试验

CTR20130893

/ Completed临床1期

氟莱哌素注射液Ⅰ期临床试验（持续72h给药）

1)确定本品持续72h给药在人体的耐受性及在人体的剂量限制性毒性2)考察氟莱哌素及其代谢物药代动力学行为3)探讨本品剂量、药代动力学参数与药效的关系4)初步考察氟莱哌素疗效5)为Ⅱ期临床研究提供安全有效的合理方案

开始日期-

申办/合作机构-

CTR20130888

/ Recruiting临床1期

氟莱哌素注射液联合培美曲赛治疗晚期NSCLC剂量探索I期临床试验

(1)确定联合给药下氟莱哌素注射液的剂量；(2)确定联合方案的MTD、DLT；(3)考察药代动力学行为并计算药代动力学参数。(4)评估耐受性和安全性。(5)初步考察联合给药的疗效。(6)为Ⅱ期临床提供安全有效的合理方案。

开始日期-

申办/合作机构-

NCT01361529

/ Unknown status临床1期

Phase 1 Study of FLP Injection on Tumor Patients

The purpose of this study is to determine the tolerance and maximum tolerated dose (MTD) for FLP Injection with multiple dose in tumor patients.

开始日期2009-06-01

申办/合作机构

安捷伦生物（杭州）有限公司

100 项与氟莱哌素相关的临床结果

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100 项与氟莱哌素相关的转化医学

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100 项与氟莱哌素相关的专利（医药）

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75

项与氟莱哌素相关的文献（医药）

2025-02-01·Journal of Ethnopharmacology

Traditional Chinese herbal formula, Fuzi-Lizhong pill, produces antidepressant-like effects in chronic restraint stress mice through systemic pharmacology

Article

作者: Zhao, Fangyi ; Cheng, Ziqian ; Chen, Hongyu ; Song, Jinfang ; Cui, Ranji ; Piao, Jingjing ; Geng, Zihui ; Li, Bingjin

ETHNOPHARMACOLOGICAL RELEVANCEFuzi-Lizhong pill (FLP) is a well-validated traditional Chinese medicine (TCM) formula that has long been used in China for gastrointestinal disease and adjunctive therapy for depression. In our previous study, we reported that the principal herb of FLP, Aconitum carmichaelii Debx. (Fuzi), exhibits antidepressant-like effects. However, there have been no reports on whether FLP produces antidepressant-like effects and its potential molecular mechanisms.AIM OF THE STUDYWe aim to demonstrate the antidepressant-like effects of FLP in chronic restraint stress (CRS) mice and to explore the associated molecular mechanisms.MATERIALS AND METHODSThe active components and probable molecular targets of FLP, as well as the targets related to depression, were identified through network pharmacology. A protein-protein interaction (PPI) network was generated using the overlapping targets, followed by the visualization as well as identification of the core targets associated with the antidepressant-like action of FLP. Subsequently, KEGG and GO enrichment analyses were conducted. UHPLC-MS/MS was employed to further detect the active compounds in FLP. Molecular docking was applied to assess the connections between the active components as well as the core targets. The efficacy of FLP in treating depression and its molecular mechanisms were examined using western blotting, ELISA, 16S rRNA sequencing, HE staining, Nissl staining, and Golgi-Cox staining in a CRS-induced mouse model.RESULTSNetwork pharmacology and UHPLC-MS/MS analyses indicated that the active compounds of FLP comprised taraxerol, songorine, neokadsuranic acid B, ginkgetin, hispaglabridin B, quercetin, benzoylmesaconine and liquiritin. KEGG pathway analysis implicated that the PI3K/Akt/mTOR as well as MAPK signaling pathways are closely related to the therapeutic effects of FLP on depression. Molecular docking analysis demonstrated that the main components of FLP bind to PI3K, AKT, mTOR, BDNF and MAPK. FLP significantly decreased immobility in mice that were elevated by CRS in the FST and the TST. FLP also significantly increased sucrose preference in mice after CRS in the SPT. FLP upregulated proteins associated with BDNF-TrkB and PI3K/Akt/mTOR signaling and downregulated proteins associated with MAPK signaling. Serum levels of CORT, IL-6, IL-1β, and TNF-α in CRS mice were significantly decreased following treatment with FLP. In addition, FLP ameliorated CRS-induced gut microbiota dysbiosis as demonstrated by 16S rRNA sequencing analysis. FLP ameliorated CRS-induced intestinal inflammation and neuronal damage. Finally, antidepressant-like effects and concomitant increases in dendritic spine density induced by FLP administration were also reduced after rapamycin treatment.CONCLUSIONThese results demonstrate that FLP has antidepressant-like effects in mice exposed to CRS that involve activation of the PI3K/Akt/mTOR signaling pathway, increase in spinogenesis, inhibition of the MAPK signaling pathway, decrease in inflammation, and amelioration of gut microbiota dysbiosis. These findings provide novel evidence for the clinical application of FLP on depression.

2024-11-01·Pesticide Biochemistry and Physiology

Integrated transcriptome and 1H NMR-based metabolome to explore the potential mechanism of Spodoptera litura in response to flupyrimin

Article

作者: Zhong, Hong ; Liu, Ying-Xue ; Lu, Zhan-Jun ; Yuan, Xiao-Fang ; Xiao, Zhao-Ying ; Xia, Zhao-Ying ; Chen, Wei ; Yu, Hai-Zhong ; Deng, Ming-Jie ; Liu, Xiao-Qiang ; Zhou, Gu-Chun

Flupyrimin (FLP) is a novel class of insecticide acting on insect nicotinic acetylcholine receptor (nAChR) and shows robust insecticidal activity. However, the toxicological effects of FLP on Spodoptera litura have not been revealed. In this study, the results showed that the larval survival rate decreased significantly with increasing concentration of FLP. The hematoxylin-eosin (HE) staining showed that FLP exposure damages the structure of the larval midgut. Additionally, FLP treatments significantly increased the activities of detoxification (GST and CarE) and digestive (α-Amylase and Trypsin) enzymes and reduced lipase activity. Transcriptome sequencing identified 855, 1493 and 735 differentially expressed genes (DEGs) at 12 h, 24 h and 48 h after exposure to 3 mM FLP, respectively. Gene function enrichment analysis revealed that DEGs were mainly related to fatty acid metabolic, protein processing in the endoplasmic reticulum and drug metabolism-cytochrome P450. The DEGs associated with food digestion and detoxification was validated by reverse-transcription quantitative PCR (RT-qPCR). Furthermore, a total of fifteen energy-related metabolites were identified, among which thirteen metabolisms were significantly influenced after FLP treatment based on ¹H NMR-based metabolome analysis, including tyrosine, glucose, trehalose, malate, threonine, proline, glycine, lysine, citrate, alanine, lactate, valine, and leucine. Taken together, these results provide useful information for revealing the toxicological effect of FLP against S. litura.

2024-06-01·Klinische Monatsblätter für Augenheilkunde

Effective Focal Laser Photocoagulation for Persistent Central Serous Chorioretinopathy: A Forgotten Technique

Article

作者: Kiraly, Peter

We report a case of a patient with persistent central serous chorioretinopathy (CSC) who was on the waiting list for half-dose photodynamic therapy (PDT). As the patient's visual function began to deteriorate, patient opted for focal laser photocoagulation (FLP) targeting the presumed leakage site in the superior part of the macula. One month after the FLP treatment, there was complete resolution of SRF accompanied by improved visual function. In light of global verteporfin shortages, limited access to PDT centers, and poor efficacy from other treatment modalities, FLP emerges as an effective treatment option for CSC patients with extrafoveal leakage. Yet, many CSC patients with extrafoveal leakage, who could be effectively treated with FLP, are often merely monitored, experiencing fluctuating SRF and a gradual, irreversible vision decline. Despite FLP's historical presence in CSC treatment, our case serves as an important reminder for retinal specialists to reconsider this treatment approach in selected CSC patients.

100 项与氟莱哌素相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肺癌	临床2期	中国	ACEA Therapeutics, Inc.初创企业	2022-01-30
非小细胞肺癌	临床1期	中国	-	2013-11-13
晚期恶性实体瘤	药物发现	中国	-	2013-11-13
晚期癌症	药物发现	中国	安捷伦生物（杭州）有限公司	2009-06-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2006	临床3期	进展期胃腺癌一线	220	FLO	齋範繭簾襯糧繭壓鏇築(鹹鏇築鬱鑰鬱鑰鹹築艱) = 糧製艱壓築簾築構鏇構簾膚鹹艱夢範製願衊鹽 (齋願網顧願網積鏇醖顧 ) 更多	积极	2006-06-20
				FLP	齋範繭簾襯糧繭壓鏇築(鹹鏇築鬱鑰鬱鑰鹹築艱) = 製襯築願獵鑰繭鹽遞獵簾膚鹹艱夢範製願衊鹽 (齋願網顧願網積鏇醖顧 ) 更多
ASCO2004	N/A	复发性胃癌一线	111	FLP	(積艱憲築選簾餘範顧鏇) = 願選壓繭鹽構衊鬱糧鬱願壓壓齋遞齋憲鏇壓襯 (築糧鑰壓鏇襯範願築鬱 ) 更多	-	2004-07-15
				S-1	(積艱憲築選簾餘範顧鏇) = 窪壓膚繭糧製襯範鬱壓願壓壓齋遞齋憲鏇壓襯 (築糧鑰壓鏇襯範願築鬱 ) 更多