PRX-08066(PRX-08066) - 药物靶点：5-HT2B receptor_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

5-HT2B receptor

作用机制

5-HT2B receptor拮抗剂(5-羟色胺2B受体拮抗剂)

治疗领域

心血管疾病呼吸系统疾病其他疾病

在研适应症-

非在研适应症

高血压肺性高血压肺动脉高压+ [1]

原研机构

Allergan Ltd. (Ireland)

在研机构-

非在研机构

Clinical Data, Inc.

EPIX Pharmaceuticals, Inc.Allergan Ltd. (Ireland)

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C19H17ClFN5S

InChIKeyIENZFHBNCRQMNP-UHFFFAOYSA-N

CAS号866206-54-4

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关联

2

项与 PRX-08066 相关的临床试验

NCT00677872 / Terminated临床2期

An Open-Label Study to Evaluate the Safety and Efficacy of PRX-08066 in Patients With Pulmonary Hypertension and Chronic Obstructive Pulmonary Disease

A 3-month open label study to evaluate the safety and efficacy of PRX-08066 in patients with pulmonary hypertension and COPD.

开始日期2008-05-01

申办/合作机构

EPIX Pharmaceuticals, Inc.

NCT00345774 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Short-Term Efficacy and Safety of PRX-08066 in Patients With Pulmonary Hypertension and Chronic Obstructive Pulmonary Disease

This study is being conducted to see if PRX-08066 can lower pulmonary artery pressures in patients with pulmonary hypertension associated with chronic obstructive pulmonary disease.

开始日期2006-06-01

申办/合作机构

EPIX Pharmaceuticals, Inc.

100 项与 PRX-08066 相关的临床结果

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100 项与 PRX-08066 相关的转化医学

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100 项与 PRX-08066 相关的专利（医药）

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4

项与 PRX-08066 相关的文献（医药）

2018-05-01·The American Journal of Pathology2区 · 医学

Effects of 5-Hydroxytryptamine Class 2 Receptor Antagonists on Bronchoconstriction and Pulmonary Remodeling Processes

2区 · 医学

Article

作者: Larsson-Callerfelt, Anna-Karin ; Rydell-Törmänen, Kristina ; Westergren-Thorsson, Gunilla ; Wenglén, Christina ; Löfdahl, Anna

Serotonin [5-hydroxytryptamine (5-HT)] is associated with several chronic pulmonary diseases, recognizing 5-HT₂ receptor antagonists as potential inhibitors of tissue remodeling. However, the effects of 5-HT₂ receptors, especially 5-HT_2B receptors on airway function and remodeling, are unclear. We investigated the role of 5-HT_2B receptors on airway smooth muscle contractility and remodeling processes. Murine precision-cut lung slices were pretreated with 5-HT_2B receptor antagonists (EXT5, EXT9, RS 127445, and PRX 08066), as well as ketanserin (5-HT_2A/2C receptor antagonist) (1, 10 μmol/L), before addition of cumulative concentrations of 5-HT to induce bronchoconstriction. Remodeling effects after treatment with 10 μmol/L 5-HT and 5-HT₂ receptor antagonists were further studied in distal lung tissue by examining release of profibrotic transforming growth factor (TGF)-β1 and proliferation of human bronchial smooth muscle cells (HBSMCs). 5-HT-induced bronchoconstriction was significantly reduced by EXT5, EXT9, and ketanserin, but not by RS 127445 or PRX 08066. The 5-HT_2B receptor antagonists significantly reduced TGF-β1 release. 5-HT, in combination with TGF-β1, increased proliferation of HBSMCs, a process reduced by EXT5 and EXT9. Our results indicate that EXT5 and EXT9 may relieve bronchoconstriction in murine airways and serve as an add-on effect in attenuating pulmonary remodeling by improving airway function. The antiproliferative effect on HBSMCs and the inhibition of TGF-β1 release further support a role of 5-HT_2B receptors in pathologic remodeling processes.

2018-03-01·Clinical & Experimental Metastasis3区 · 医学

Expression of the serotonin receptor 2B in uveal melanoma and effects of an antagonist on cell lines

3区 · 医学

Article

作者: Weidmann, Cindy ; Landreville, Solange ; Bérubé, Julie ; Piquet, Léo ; de la Fouchardière, Arnaud

Uveal melanoma (UM) is the most common primary tumor in the adult, and disseminates to the liver in half of patients. A 15-gene expression profile prognostic assay allows to determine the likelihood of metastasis in patients using their ocular tumor DNA, but a cure still remains to be discovered. The serotonin receptor 2B represents the discriminant gene of this molecular signature with the greatest impact on the prognosis of UM. However, its contribution to the metastatic potential of UM remains unexplored. The purpose of this study was to investigate the effects of a selective serotonin receptor 2B antagonist on cellular and molecular behaviours of UM cells. UM cell lines expressing high level of serotonin receptor 2B proteins were selected by Western blotting. The selective serotonin receptor 2B antagonist PRX-08066 was evaluated for its impact on UM cells using viability assays, phosphorylated histone H3 immunostainings, clonogenic assays, migration assays, invasion assays and membrane-based protein kinase phosphorylation antibody arrays. The pharmacological inhibition of the serotonin receptor 2B reduced the viability of UM cells and the population in mitosis, and impaired their clonogenicity and potential of migration. It also decreased the phosphorylation of kinases from signaling pathways classically activated by the serotonin receptor 2B, as well as kinases β-catenin, Proline-rich tyrosine kinase 2, and Signal transducer and activator of transcription 5. Our findings support a role for the serotonin receptor 2B in the proliferation and migration of UM cells, through activation of many signaling pathways such as WNT, Focal adhesion kinase and Janus kinase/STAT.

2010-08-01·Journal of Pharmacology and Experimental Therapeutics3区 · 医学

PRX-08066, a Novel 5-Hydroxytryptamine Receptor 2B Antagonist, Reduces Monocrotaline-Induced Pulmonary Arterial Hypertension and Right Ventricular Hypertrophy in Rats

3区 · 医学

Article

作者: Jacques, Vincent ; Byrne, Barry J. ; Porvasnik, Stacy L. ; Gannon, Kimberley S. ; Shacham, Sharon ; Al-Mousily, Faris ; Germain, Sean ; Embury, Jennifer ; Murray, Justin

Pulmonary arterial hypertension (PAH) is a life-threatening disease that results in right ventricular failure. 5-((4-(6-Chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile monofumarate (PRX-08066) is a selective 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist that causes selective vasodilation of pulmonary arteries. In the current study, the effects of PRX-08066 were assessed by using the monocrotaline (MCT)-induced PAH rat model. Male rats received 40 mg/kg MCT or phosphate-buffered saline and were treated orally twice a day with vehicle or 50 or 100 mg/kg PRX-08066 for 5 weeks. Pulmonary and cardiac functions were evaluated by hemodynamics, heart weight, magnetic resonance imaging (MRI), pulmonary artery (PA) morphology, and histology. Cardiac MRI demonstrated that PRX-08066 (100 mg/kg) significantly (P < 0.05) improved right ventricular ejection fraction. PRX-08066 significantly reduced peak PA pressure at 50 and 100 mg/kg (P < 0.05 and < 0.01, respectively) compared with MCT control animals. PRX-08066 therapy also significantly reduced right ventricle (RV)/body weight and RV/left ventricle + septum (P < 0.01 and < 0.001, respectively) compared with MCT-treated animals. Morphometric assessment of pulmonary arterioles revealed a significant reduction in medial wall thickening and lumen occlusion associated with both doses of PRX-08066 (P < 0.01). The 5-HT2BR antagonist PRX-08066 significantly attenuated the elevation in PA pressure and RV hypertrophy and maintained cardiac function. Pulmonary vascular remodeling was also diminished compared with MCT control rats. PRX-08066 prevents the severity of PAH in the MCT rat model.

100 项与 PRX-08066 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	PRX-08066	-	DB05607

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
肺性高血压	临床2期	美国	EPIX Pharmaceuticals, Inc.	2006-06-01
慢性阻塞性肺疾病	临床2期	美国	EPIX Pharmaceuticals, Inc.	2006-06-01
高血压	临床2期	-	Allergan Ltd. (Ireland)	-
肺动脉高压	临床2期	美国	Clinical Data, Inc.	-