Delving into the Latest Updates on Taprenepag isopropyl with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Taprenepag, Taprenepag isopropyl (USAN)

+ [3]

Target

EP2 x Opioid receptors

Action

agonists

Mechanism

EP2 agonists(Prostanoid EP2 receptor agonists), Opioid receptors agonists(Opioid receptors agonists)

Therapeutic Areas

Eye Diseases

Active Indication-

Inactive Indication

Glaucoma, Open-Angle

Originator Organization

Pfizer Inc.

Active Organization-

Inactive Organization

Pfizer Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC27H28N4O5S

InChIKeyNVPXUFQLKWKBHK-UHFFFAOYSA-N

CAS Registry1005549-94-9

View All Structures (2)

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.

01 Oct 2022·Prostaglandins & Other Lipid Mediators

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

Article

Author: 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.

03 May 2022·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

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

Q1 · CROSS-FIELD

Article

Author: 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 Deals associated with Taprenepag isopropyl

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External Link

KEGG	Wiki	ATC	Drug Bank
D09969	-	-	DB12623

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glaucoma, Open-Angle	Phase 2	United States	Pfizer Inc.	11 Dec 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00934089 (CTgov)	Phase 2	Glaucoma, Open-Angle	31	Taprenepag+Latanoprost (Taprenepag+Latanoprost)	rbrlaxdxko(mfuuiqxtmf) = ojzhmrqxke pseeiduxqz (klrxpvrabw, hxcdoprjkx - icqdwpiexn) View more	-	03 May 2021
				Taprenepag+Latanoprost (Taprenepag+Latanoprost Vehicle)	rbrlaxdxko(mfuuiqxtmf) = btjvumdjlf pseeiduxqz (klrxpvrabw, xoufbgfyxi - emgnabbvks) View more
NCT00934089 (ARVO2011)	Phase 2	-	30	Taprenepag Isopropyl 0.01%	(xciyqmrltq) = oylpxtbfkb jyoqoghhbu (vjkjaooocq ) View more	-	01 Apr 2011
				Taprenepag Isopropyl 0.01% + Latanoprost 0.005%	(xciyqmrltq) = eenkxsyqig jyoqoghhbu (vjkjaooocq ) View more
NCT00572455 (ARVO2010)	Phase 1	Ocular Hypotension	67	PF-04217329 0.0025%	qlptgmrkjo(zmmnqbczod) = malubgmita olplmofljr (kzeagwnenz )	Positive	01 Apr 2010
				PF-04217329 0.005%	qlptgmrkjo(zmmnqbczod) = iudwnynxds olplmofljr (kzeagwnenz )