Taprenepag isopropyl(Taprenepag isopropyl) - 药物靶点：EP2 x Opioid receptors_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Taprenepag、Taprenepag isopropyl (USAN)

+ [3]

靶点

EP2 x Opioid receptors

作用方式

激动剂

作用机制

EP2激动剂(前列腺素EP2受体激动剂)、Opioid receptors激动剂(阿片样受体激动剂)

治疗领域

眼部疾病

在研适应症-

非在研适应症

开角型青光眼

原研机构

Pfizer Inc.

在研机构-

非在研机构

Pfizer Inc.

最高研发阶段无进展临床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/序列

分子式C27H28N4O5S

InChIKeyNVPXUFQLKWKBHK-UHFFFAOYSA-N

CAS号1005549-94-9

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关联

4

项与 Taprenepag isopropyl 相关的临床试验

ACTRN12612000880842

/ Completed临床1期

A Phase 1, Single-Center, Dose-Ranging, Multi-Treatment Study to Determine the Safety and Pharmacokinetics of Single Oral Dose Combinations of PF329 and Nafamostat Mesilate in Healthy Subjects

开始日期2012-09-24

申办/合作机构

Signature Therapeutics, Inc.

ACTRN12610000721000

/ Completed临床1期

A Phase 1, Single-Center, Dose-Escalation and Fixed-Dose Crossover, Cohort Study to Determine the Safety and Pharmacokinetics of a Single Oral Dose of PF329 versus oral hydromorphone hydrochloride (HCl) in Healthy Subjects

开始日期2010-10-25

申办/合作机构-

NCT00934089

/ Completed临床2期

A Phase 2, Single-masked, Randomized, Crossover Study Of The 24-hour Intraocular Pressure Lowering And Systemic Exposure of Pf-04217329 Alone And In Combination With Latanoprost

This study will characterize the effect of PF-04217329, alone and in combination with latanoprost, on circadian intraocular pressure and blood pressure in glaucoma patients. Blood samples will be collected to measure the amount of active metabolite of PF-04217329 in the plasma following dosing.

开始日期2010-01-01

申办/合作机构

Pfizer Inc.

100 项与 Taprenepag isopropyl 相关的临床结果

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100 项与 Taprenepag isopropyl 相关的转化医学

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100 项与 Taprenepag isopropyl 相关的专利（医药）

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18

项与 Taprenepag isopropyl 相关的文献（医药）

2023-10-01·Journal of Ocular Pharmacology and Therapeutics

Ocular Treatments Targeting Separate Prostaglandin Receptors in Mice Exhibit Alterations in Intraocular Pressure and Optic Nerve Lipidome

Article

作者: Sharif, Najam A ; Arcuri, Jennifer ; Elbaz, Abdelrahman ; Bhattacharya, Sanjoy K

Background: Prostaglandin (PG) receptor agonists are the first-line eyedrop medication treatment for glaucoma. The pathophysiology of this disease is not completely known, and elevated intraocular pressure (IOP) is the key risk factor. The membranes of the axons (of the retinal ganglion cells) passing through the optic nerve (ON) head experience significant damage. Lipids are an essential component of the cell's membranes, and their profile changes owing to neurodegeneration. In this investigation, three agonists for distinct PG receptors were used to lower IOP and to determine their effect on the ON lipids. We utilized DBA/2J mice as a model of progressive IOP increase and C57BL/6J mice as a model of ON crush. Methods: DBA/2J and C57BL/6J mice were treated daily for 2 weeks with Latanoprost, PF-04217329, or Rivenprost. The IOP was measured every 2 days and pattern electroretinogram was conducted for DBA/2J throughout the study. Lipidomics of ONs were performed for each model and treatment group. Results: Of the tested compounds, Latanoprost and Rivenprost were the most effective agents decreasing IOP in DBA/2J mice. Triglyceride levels increased in the ONs of DBA/2J mouse model, but phosphatidylethanolamine levels underwent highest level changes in the C57BL/6J mouse model when treated with Latanoprost. Conclusions: Topical ocular FP- and EP4-receptor agonists appreciably lowered IOP in the DBA/2J mice representing pigmentary glaucoma. The observed changes in ON lipidomics in the different models of neurodegeneration suggest possible use of such measures in the development of more effective medicines for both IOP reduction and ON protection.

2022-10-01·Prostaglandins & Other Lipid Mediators

The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms

Article

作者: Singh, Nalin ; Barnych, Bogdan ; Matsumoto, Naoki ; Morisseau, Christophe ; Lee, Kin Sing ; Hammock, Bruce D

The cellular mechanism by which epoxy fatty acids (EpFA) improves disease status is not well characterized. Previous studies suggest the involvement of cellular receptors and cyclic AMP (cAMP). Herein, the action of EpFAs derived from linoleic acid (LA), arachidonic acid (ARA), and docosahexaenoic acid on cAMP levels was studied in multiple cell types to elucidate relationships between EpFAs, receptors and cells' origin. cAMP levels were enhanced in HEK293 and LLC-PK1 cells by EpFAs from LA and ARA. Using selective antagonists, the EpFA effects on cAMP levels appear dependent on the prostaglandin E₂ receptor 2 (EP2) but not 4 (EP4). Human coronary artery smooth muscle cells responded similarly to the EpFAs. However, we were not able to show the involvement of any of the receptors tested in this cell type. The results pinpointed distinct cell lines and receptor subtypes that natively respond to EpFA.

2022-05-03·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Agonists of prostaglandin E ₂ receptors as potential first in class treatment for nephronophthisis and related ciliopathies

1区 · 综合性期刊

Article

作者: Saunier, Sophie ; Porée, Esther ; Delous, Marion ; Krug, Pauline ; Fila, Marc ; Salomon, Rémi ; Garcia, Hugo ; Briseño-Roa, Luis ; Viau, Amandine ; Serafin, Alice S. ; Sin-Monnot, Soraya ; Cagnard, Nicolas ; Lyonnet, Stanislas ; Billot, Katy ; Annereau, Jean-Philippe ; Del Nery, Elaine ; Benmerah, Alexandre ; Mahaut, Clémentine ; Silbermann, Flora ; Roy, Stéphanie ; Garfa-Traore, Meriem ; Birgy, Éléonore ; Antignac, Corinne ; Deleglise, Bérangère ; Rodriguez, Pamela C. ; Jabot-Hanin, Fabienne ; Mehraz, Manon ; Ceccarelli, Salomé ; Furio, Laetitia

Nephronophthisis (NPH) is an autosomal recessive tubulointerstitial nephropathy belonging to the ciliopathy disorders and known as the most common cause of hereditary end-stage renal disease in children. Yet, no curative treatment is available. The major gene, NPHP1, encodes a protein playing key functions at the primary cilium and cellular junctions. Using a medium-throughput drug-screen in NPHP1 knockdown cells, we identified 51 Food and Drug Administration-approved compounds by their ability to alleviate the cellular phenotypes associated with the loss of NPHP1; 11 compounds were further selected for their physicochemical properties. Among those compounds, prostaglandin E1 (PGE1) rescued ciliogenesis defects in immortalized patient NPHP1 urine-derived renal tubular cells, and improved ciliary and kidney phenotypes in our NPH zebrafish and Nphp1 knockout mouse models. Furthermore, Taprenepag, a nonprostanoid prostaglandin E2 receptor agonist, alleviated the severe retinopathy observed in Nphp1−/− mice. Finally, comparative transcriptomics allowed identification of key signaling pathways downstream PGE1, including cell cycle progression, extracellular matrix, adhesion, or actin cytoskeleton organization. In conclusion, using in vitro and in vivo models, we showed that prostaglandin E2 receptor agonists can ameliorate several of the pleotropic phenotypes caused by the absence of NPHP1; this opens their potential as a first therapeutic option for juvenile NPH-associated ciliopathies.

100 项与 Taprenepag isopropyl 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09969	-	-	DB12623

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
开角型青光眼	临床2期	美国	Pfizer Inc.	2007-12-11

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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


NCT00934089 (CTgov)	临床2期	开角型青光眼	31	Taprenepag+Latanoprost (Taprenepag+Latanoprost)	衊憲壓選製顧膚鏇繭簾(艱範鬱構積艱蓋繭築鏇) = 憲鏇鑰鹹鹹廠範壓鑰醖遞糧憲壓選繭壓糧鏇簾 (齋廠餘憲鏇糧鑰蓋餘簾, 繭蓋構構壓鏇窪衊艱顧 ~ 醖襯壓憲繭構窪遞積構) 更多	-	2021-05-03
				Taprenepag+Latanoprost (Taprenepag+Latanoprost Vehicle)	衊憲壓選製顧膚鏇繭簾(艱範鬱構積艱蓋繭築鏇) = 網膚鏇積鹹鬱夢齋構餘遞糧憲壓選繭壓糧鏇簾 (齋廠餘憲鏇糧鑰蓋餘簾, 膚製襯膚鏇壓網網廠壓 ~ 夢鏇廠襯顧簾鹹夢鏇醖) 更多
NCT00934089 (ARVO2011)	临床2期	-	30	Taprenepag Isopropyl 0.01%	(餘網廠壓積繭夢壓蓋膚) = 鏇獵願顧淵網繭糧窪簾鏇醖廠構選齋艱選選築 (廠壓憲網醖衊網選淵願 ) 更多	-	2011-04-01
				Taprenepag Isopropyl 0.01% + Latanoprost 0.005%	(餘網廠壓積繭夢壓蓋膚) = 夢齋繭網壓壓選鏇鏇襯鏇醖廠構選齋艱選選築 (廠壓憲網醖衊網選淵願 ) 更多
NCT00572455 (ARVO2010)	临床1期	低眼压	67	PF-04217329 0.0025%	餘糧構鏇獵夢鹽範醖憲(遞艱艱構壓獵鹹膚膚鹹) = 觸築淵夢構鹹壓餘願蓋範鹽蓋夢憲鹹餘鹽鏇艱 (築鏇齋壓壓觸醖餘願簾 )	积极	2010-04-01
				PF-04217329 0.005%	餘糧構鏇獵夢鹽範醖憲(遞艱艱構壓獵鹹膚膚鹹) = 積鏇憲顧艱構襯齋蓋醖範鹽蓋夢憲鹹餘鹽鏇艱 (築鏇齋壓壓觸醖餘願簾 )