艾他洛西(Etalocib sodium) - 药物靶点：5-LOX x LTB4R x PPARγ_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Etalocib

+ [4]

靶点

5-LOX x LTB4R x PPARγ

作用机制

5-LOX抑制剂(5-脂氧合酶抑制剂)、LTB4R拮抗剂(白三烯B4受体1拮抗剂)、PPARγ激动剂(过氧化物酶体增长因子活化受体γ激动剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [1]

在研适应症-

非在研适应症

非小细胞肺癌胰腺癌

原研机构

Eli Lilly & Co.

在研机构-

非在研机构

Eli Lilly & Co.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C33H33FNaO6

InChIKeyIIAIFGQWVPLOLQ-UHFFFAOYSA-N

CAS号152608-41-8

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关联

3

项与艾他洛西相关的临床试验

NCT00069875 / Completed临床2期

Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study of Gemcitabine-Cisplatin Combined With Two Different Doses of LY293111 or Placebo in Patients With Stage IIIB or IV Non-Small Cell Lung Cancer

The purpose of this study is to determine the effectiveness and side effects of LY293111 given in combination with gemcitabine and cisplatin in patients with non-small cell lung cancer.

开始日期2003-09-01

申办/合作机构

Eli Lilly & Co.

NCT00055250 / Completed临床2期

A Randomized, Placebo-Controlled, Double-Blind Phase 2 Study of Gemcitabine Plus LY293111 Compared to Gemcitabine Plus Placebo in Patients With Locally Advanced or Metastatic Pancreatic Cancer

The purpose of this study is to determine the effectiveness and side effects of LY293111 given in combination with gemcitabine in patients with pancreatic cancer.

开始日期2003-01-01

申办/合作机构

Eli Lilly & Co.

NCT00006375 / Completed临床1期IIT

A Phase I Clinical and Pharmacokinetic Evaluation of LY293111 in Patients With Solid Tumors (Protocol H6H-MC-JEAI)

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of LY293111 in treating patients who have advanced solid tumors.

开始日期2000-06-01

申办/合作机构

Memorial Sloan Kettering Cancer Center

[+1]

100 项与艾他洛西相关的临床结果

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100 项与艾他洛西相关的转化医学

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100 项与艾他洛西相关的专利（医药）

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37

项与艾他洛西相关的文献（医药）

2024-05-01·European Journal of Immunology

Leukotriene B4‐induced neutrophil extracellular traps impede the clearance of Pneumocystis

Article

作者: Zhou, Yanxi ; Zhang, Yue ; Du, Chunjing ; Li, Lan ; Wang, Yijie ; Zhang, Liang ; Deng, Shuwei ; Liu, Yujia ; Zhu, Liuluan

AbstractPneumocystis pneumonia (PCP) is a fungal pulmonary disease with high mortality in immunocompromised patients. Neutrophils are essential in defending against fungal infections; however, their role in PCP is controversial. Here we aim to investigate the effects of neutrophil extracellular traps (NETs) on Pneumocystis clearance and lung injury using a mouse model of PCP. Intriguingly, although neutrophils play a fundamental role in defending against fungal infections, NETs failed to eliminate Pneumocystis, but instead impaired the killing of Pneumocystis. Mechanically, Pneumocystis triggered Leukotriene B4 (LTB4)‐dependent neutrophil swarming, leading to agglutinative NET formation. Blocking Leukotriene B4 with its receptor antagonist Etalocib significantly reduced the accumulation and NET release of neutrophils in vitro and in vivo, enhanced the killing ability of neutrophils against Pneumocystis, and alleviated lung injury in PCP mice. This study identifies the deleterious role of agglutinative NETs in Pneumocystis infection and reveals a new way to prevent NET formation, which provides new insights into the pathogenesis of PCP.

2020-07-01·The Ocular Surface2区 · 医学

RvE1 uses the LTB4 receptor BLT1 to increase [Ca2+]i and stimulate mucin secretion in cultured rat and human conjunctival goblet cells

2区 · 医学

Article

作者: Serhan, Charles N ; Fjærvoll, Haakon K ; Utheim, Tor P ; Fjærvoll, Ketil A ; Bair, Jeffery A ; Yang, Menglu ; Hodges, Robin R ; Lippestad, Marit ; Dartt, Darlene A

PURPOSESpecialized pro-resolving lipid mediator resolvin (Rv) E1 stimulates secretion including mucins from conjunctival goblet cells. RvE1 can use both its ChemR23 receptor and the LTB₄ receptor BLT1 to increase [Ca²⁺]_i. The purpose of this study was to determine the expression of ChemR23 and BLT1 and receptors on conjunctival goblet cells and the respective roles these two receptors play in goblet cell responses to RvE1.METHODSGoblet cells were cultured from male rat or human conjunctiva from both sexes. Western blotting analysis, reverse transcription PCR and immunofluorescence microscopy were used to demonstrate the expression of ChemR23 and BLT1 in conjunctival goblet cells. High molecular weight glycoprotein secretion was determined using an enzyme-linked lectin assay. Signaling pathways were studied by measuring the increase in [Ca²⁺]_i using fura 2/AM.RESULTSChemR23 and BLT1 and receptors were present on both rat and human conjunctival goblet cells. The BLT1 inhibitors LY293111 and U75302 significantly blocked RvE1-and LTB₄-stimulated [Ca²⁺]_i increase. RvE1-and LTB₄-stimulated [Ca²⁺]_i and secretion increases were blocked by BLT1-targeted siRNA. RvE1-stimulated [Ca²⁺]_i and secretion increases were also blocked by ChemR23-targeted siRNA. Addition of RvE1 2 min before or simultaneously with LTB₄ desensitized the LTB₄ [Ca²⁺]_i response. Addition of RvE1 and LTB₄ simultaneously caused secretion that was decreased compared to either response alone.CONCLUSIONRvE1, in addition to the ChemR23 receptor, uses the BLT1 receptor to increase [Ca²⁺]_i and stimulate secretion in both rat and human cultured conjunctival goblet cells.

2018-04-01·International Immunopharmacology2区 · 医学

Substance P-regulated leukotriene B4 production promotes acute pancreatitis-associated lung injury through neutrophil reverse migration

2区 · 医学

Article

作者: Wu, Zengkai ; Hu, Guoyong ; Wan, Rong ; Han, Xiao ; Li, Bin ; Dai, Juanjuan ; Ye, Xin ; Chen, Congying ; Ni, Jianbo ; Wang, Xingpeng ; Wu, Jianghong

Leukotriene B4 (LTB4) is a potent chemoattractant and inflammatory mediator involved in multiple inflammatory diseases. Substance P (SP) has been reported to promote production of LTB4 in itch-associated response in vivo and in some immune cells in vitro. Here, we investigated the role of LTB4 in acute pancreatitis (AP), AP-associated acute lung injury (ALI) and the related mechanisms of LTB4 production in AP. In vivo, murine AP model was induced by caerulein and lipopolysaccharide or L-arginine. The levels of LTB4 and its specific receptor BLT1 were markedly upregulated in both AP models. Blockade of BLT1 by LY293111 attenuated the severity of AP, decreased neutrophil reverse transendothelial cell migration (rTEM) into the circulation and alleviated the severity of ALI. In vitro, treatment of pancreatic acinar cells with SP increased LTB4 production. Furthermore, SP treatment increased phosphorylation of protein kinase C (PKC) α and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p-38 MAPK and c-Jun NH2-terminal kinase (JNK). Finally, blockade of neurokinin-1 receptor by CP96345 significantly attenuated the severity of AP and decreased the level of LTB4 when compared to AP group. In summary, these results show that SP regulates the production of LTB4 via PKCα/MAPK pathway, which further promotes AP-associated ALI through neutrophil rTEM.

100 项与艾他洛西相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	艾他洛西	-	DB12850

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
非小细胞肺癌	临床2期	以色列	Eli Lilly & Co.	2003-09-01
非小细胞肺癌	临床2期	美国	Eli Lilly & Co.	2003-09-01
非小细胞肺癌	临床2期	德国	Eli Lilly & Co.	2003-09-01
非小细胞肺癌	临床2期	加拿大	Eli Lilly & Co.	2003-09-01
非小细胞肺癌	临床2期	荷兰	Eli Lilly & Co.	2003-09-01
非小细胞肺癌	临床2期	西班牙	Eli Lilly & Co.	2003-09-01
胰腺癌	临床2期	美国	Eli Lilly & Co.	2003-01-01

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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2期	晚期非小细胞肺癌	201	LY293111 200 mg BID	(艱範衊網顧憲獵選鏇蓋) = 鹽醖範蓋獵顧淵構選製廠積積窪鹹網壓積窪餘 (鬱觸廠鹹鏇鑰糧齋築壓 ) 更多	不佳	2006-06-20
				LY293111 600 mg BID	(艱範衊網顧憲獵選鏇蓋) = 獵淵衊構築衊獵壓膚鏇廠積積窪鹹網壓積窪餘 (鬱觸廠鹹鏇鑰糧齋築壓 ) 更多