Delving into the Latest Updates on PF-04191834 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

5-LOX

Mechanism

5-LOX inhibitors(Arachidonate 5-lipoxygenase inhibitors)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesRespiratory Diseases+ [1]

Active Indication-

Inactive Indication

AsthmaOsteoarthritis, KneePain

Originator Organization

Pfizer Inc.

Active Organization-

Inactive Organization

Pfizer Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC22H23N3O2S

InChIKeyDVNQWYLVSNPCJZ-UHFFFAOYSA-N

CAS Registry1029317-21-2

This study investigates the safety, tolerability and pharmacokinetics of PF-04191834 when respectively given orally as a single dispersion dose and a single dose of a suspension. The suspension is the test formulation and the dispersion is the formulation with which the novel preparation will be compared.

Start Date01 Dec 2010

Sponsor / Collaborator

Pfizer Inc.

NCT01147458 / TerminatedPhase 2

A Phase 2 Randomized, Double-Blinded, Double-Dummy, Placebo And Active Controlled Two Cohort Two-Way Cross-Over, Multi-Centre Clinical Trial To Examine The Pain Relief Produced By 2 Weeks Of Daily Oral Administration Of A 5-Lipoxygenase (5-Lox) Inhibitor PF-04191834 Alone And In Combination With Naproxen In Patients With Flare-Enriched Osteoarthritis Of The Knee

PF-04191834 works in animal models by inhibiting one of the enzymes, 5-lipoxygenasein which is involved in the pathway that causes inflammation and pain. The purpose of this study is to test how effective, safe and tolerated PF-04191834 is in patients with osteoarthritis of the knee by itself or with naproxen, particularly to test if patients have less pain.

Start Date01 Jul 2010

Sponsor / Collaborator

Pfizer Inc.

NCT01064804 / CompletedNot Applicable

An Open Randomised 4-Way Crossover Single Dose And A Parallel Group Multiple Dose Comparative Pharmacokinetic Study Of The PF-04191834 Phase 2 Tablet And The Phase 1 Dispersion Formulations.

To test the relative bioavailability of PF-04191834 when dosed as an Immediate Release tablet compared with solution following single and multiple dosing.

Start Date01 Sep 2009

Sponsor / Collaborator

Pfizer Inc.

100 Clinical Results associated with PF-04191834

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100 Translational Medicine associated with PF-04191834

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100 Patents (Medical) associated with PF-04191834

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4

Literatures (Medical) associated with PF-04191834

01 Dec 2021·Cytokine & Growth Factor ReviewsQ2 · MEDICINE

The role and transformative potential of IL-19 in atherosclerosis

Q2 · MEDICINE

Review

Author: Jiyao Xing ; Xinlin Liu ; Wujun Chen ; Dongming Xing ; Shuai Wang

Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Traditionally, IL-19 was thought to be expressed in only immune cells, but studies revealed that IL-19 is also expressed in multiple atherosclerotic plaque cell types, but not normal arteries, in humans and mice. IL-19 reduces the development of atherosclerosis via multiple mechanisms, including balancing cholesterol metabolism; enhancing Th2 immune cell polarization; reducing the inflammatory response; and reducing the proliferation, migration and chemotaxis of vascular smooth muscle cells (VSMCs). Clinical and/or animal studies have primarily aimed to achieve regression and/or stabilization of atherosclerotic plaques, with regression in particular indicating a very good drug response. Most antiatherosclerotic drugs in current clinical use, including atorvastatin and alirocumab, target hyperlipidemia. Several other drugs have also been investigated in clinical trials as anti-inflammatory agents; the development of some of these agents has been terminated (canakinumab, darapladib, varespladib, losmapimod, atreleuton, setileuton, PF-04191834, veliﬂapon, and methotrexate), but others remain in development (ziltivekimab, tocilizumab, Somalix, IFM-2427, anakinra, mesenchymal stem cells (MSCs), colchicine, everolimus, allopurinol, and montelukast). Most of the tested drugs have shown a limited ability to reverse atherosclerosis in animal studies. Interestingly, recombinant IL-19 (rIL-19) was shown to reduce atherosclerosis development in a time- and dose-dependent manner. A low dose of rIL-19 (1 ng/g/day) reduced aortic arch and root plaque areas by 70.1% and 32.1%, respectively, in LDLR^-/- mice. At 10 ng/g/day, rIL-19 completely eliminated atherosclerotic plaques. There were no sex differences in the effects of rIL-19 on atherosclerotic mice. Thus, low-dose rIL-19 is an effective antiatherosclerotic agent, in addition to its efficacy in intimal hyperplasia, spinal cord injury, stroke, and multiple sclerosis. We propose that IL-19 is a promising biomarker and target for the diagnosis and treatment of atherosclerosis. This review considers the role and mechanism of action of IL-19 in atherosclerosis and discusses whether IL-19 is a potential therapeutic target for this condition.

01 Jul 2010·Journal of Pharmacology and Experimental TherapeuticsQ3 · MEDICINE

Pharmacology of PF-4191834, a Novel, Selective Non-Redox 5-Lipoxygenase Inhibitor Effective in Inflammation and Pain

Q3 · MEDICINE

Article

Author: Dufield, Dawn ; Hardy, Medora ; Pufahl, Robert A. ; Anderson, Gary D. ; Zweifel, Ben S. ; Cortes-Burgos, Luz ; Graneto, Matthew ; Masferrer, Jaime L.

5-Lipoxygenase (LOX) is an important arachidonic acid-metabolizing enzyme producing leukotrienes and other proinflammatory lipid mediators with potent pathophysiological functions in asthma and other inflammatory diseases. 4-(3-(4-(1-Methyl-1H-pyrazol-5-yl)phenylthio)phenyl)-tetrahydro-2H-pyran-4-carboxamide (PF-4191834) is a novel, selective non-redox 5-lipoxygenase inhibitor effective in inflammation and pain. In vitro and in vivo assays were developed for the evaluation of a novel 5-LOX inhibitor using conditions of maximal enzyme activity. PF-4191834 exhibits good potency in enzyme- and cell-based assays, as well as in a rat model of acute inflammation. Enzyme assay results indicate that PF-4191834 is a potent 5-LOX inhibitor, with an IC(50) = 229 +/- 20 nM. Furthermore, it demonstrated approximately 300-fold selectivity for 5-LOX over 12-LOX and 15-LOX and shows no activity toward the cyclooxygenase enzymes. In addition, PF-4191834 inhibits 5-LOX in human blood cells, with an IC(80) = 370 +/- 20 nM. This inhibitory concentration correlates well with plasma exposures needed for in vivo efficacy in inflammation in models of inflammatory pain. The combination of potency in cells and in vivo, together with a sustained in vivo effect, provides PF-4191834 with an overall pharmacodynamic improvement consistent with once a day dosing.

Chemical ScienceQ1 · CHEMISTRY

Electrophilic fluoroalkylthiolation induced diastereoselective and stereospecific 1,2-metalate migration of alkenylboronate complexes

Q1 · CHEMISTRY

ArticleOA

Author: Lu, Long ; Shen, Qilong ; Shen, Feng

A transition metal free process for conjunctive functionalization of alkenylboron ate-complexes with electrophilic fluoroalkylthiolating reagents affords β-tri- and difluoroalkylthiolated boronic esters in good yield and diastereoselectivity.

100 Deals associated with PF-04191834

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11645

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoarthritis, Knee	Phase 2	CA	Pfizer Inc.	01 Jul 2010
Osteoarthritis, Knee	Phase 2	SE	Pfizer Inc.	01 Jul 2010
Osteoarthritis, Knee	Phase 2	US	Pfizer Inc.	01 Jul 2010
Pain	Phase 2	US	Pfizer Inc.	01 Jul 2010
Pain	Phase 2	CA	Pfizer Inc.	01 Jul 2010
Pain	Phase 2	SE	Pfizer Inc.	01 Jul 2010
Asthma	Phase 2	US	Pfizer Inc.	01 Jul 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01147458 (CTgov)	Phase 2	Pain \| Osteoarthritis, Knee	190	Naproxen placebo+PF-04191834 (PF-04191834 Followed by Placebo)	vvqywrtlyh(xaaoxfuydo) = rzttgoukuh jfvzxufsii (aukyovwmrk, rpywaogpkl - ewkgkoayig) View more	-	21 May 2013
NCT01147458 (CTgov)	Phase 2	Pain \| Osteoarthritis, Knee	190	Naproxen placebo+PF-04191834 (Placebo Followed by PF-04191834)	vvqywrtlyh(xaaoxfuydo) = pzzcdpcdjg jfvzxufsii (aukyovwmrk, ibikkgrwih - xgtktisqca) View more	-	21 May 2013
NCT00723021 (CTgov)	Phase 2	Asthma	15	Placebo	vuztmllgsc(msmxkudjlc) = mwcjmuqvfv larmnbpccm (gdohcotuwj, patcbctimm - kjnqraanqq) View more	-	01 Feb 2013