Delving into the Latest Updates on Fiboflapon Sodium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Fiboflapon, Fiboflapon sodium (USAN)

+ [4]

Target

FLAP

Action

inhibitors

Mechanism

FLAP inhibitors(5-lipoxygenase activating protein inhibitors)

Therapeutic Areas

Immune System DiseasesRespiratory DiseasesOther Diseases+ [1]

Active Indication-

Inactive Indication

AsthmaAsthma, Exercise-InducedCardiovascular Diseases+ [1]

Originator Organization

Bristol Myers Squibb Co.

Active Organization-

Inactive Organization

GSK Plc

Amira Pharmaceuticals, Inc.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC38H43N3O4S

InChIKeyDFQGDHBGRSTTHX-UHFFFAOYSA-N

CAS Registry936350-00-4

View All Structures (2)

The purpose of this study is to investigate the effect on repeat doses of GSK2190915 in asthmatic patients with a high percentage of neutrophils in their sputum. GSK2190915 will be given as an add on to current therapy, and its effects on the percentage of sputum neutrophils in the patients will be assessed.

Start Date01 Jun 2011

Sponsor / Collaborator

GSK Plc

NCT01411111

/ CompletedPhase 1

An Open Label, Sequential, Single Cohort, Repeat Dose Study to Investigate the Potential Interaction of GSK2190915 on the Pharmacokinetics of Rosuvastatin in Healthy Adult Subjects.

Leukotrienes are potent inflammatory molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in response to allergic or inflammatory stimuli. GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes, through the blockage of the first committed step in the leukotriene pathway, 5 lipoxygenase (5-LO) activation.
GSK2190915 has been shown to be an in vitro inhibitor of human organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3), hence there is a potential for a pharmacokinetic drug-drug interaction with OATP1/ B1 substrates such as the anti-lipidemic rosuvastatin.
This study will evaluate the effect of repeat oral dosing of GSK2190915 (30milligram (mg) and 100mg) on the steady-state pharmacokinetics (PK) of rosuvastatin (10 mg). In addition, the study will evaluate the safety and tolerability of this combination when co-administered to healthy, adult volunteers in two cohorts.

Start Date06 Jan 2011

Sponsor / Collaborator

GSK Plc

NCT01248975

/ CompletedPhase 2

A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Three-Treatment, Three 6-Week Period Cross-Over, Multi-Center Study to Evaluate the Effect of Adding GSK2190915 300mg as Compared to Adding Montelukast 10mg or Placebo Tablets QD to Fluticasone Propionate/Salmeterol 250/50mcg Diskus BID

The primary objective of this study is to evaluate the efficacy and safety of adding GSK2190915 300mg or placebo tablets administered once daily to fluticasone propionate/salmeterol 250/50mcg inhalation powder administered twice daily in uncontrolled asthmatic subjects > or = 18 years of age over the course of 6 weeks treatment.
The secondary objectives are to undertake an exploratory analysis of the efficacy and safety of adding montelukast 10mg administered once daily to fluticasone propionate/salmeterol 250/50mcg inhalation powder administered twice daily and to investigate the pharmacokinetics and pharmacodynamics of GSK2190915 in uncontrolled asthmatic subjects > or = 18 years of age over the course of 6 weeks treatment.

Start Date01 Dec 2010

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with Fiboflapon Sodium

Login to view more data

100 Translational Medicine associated with Fiboflapon Sodium

Login to view more data

100 Patents (Medical) associated with Fiboflapon Sodium

Login to view more data

21

Literatures (Medical) associated with Fiboflapon Sodium

01 Sep 2022·Gland Surgery

Comprehensive analysis reveals potential hub genes and therapeutic drugs in an acquired lymphedema model

Article

Author: Zhang, Yiwen ; Chen, Jiemei ; Li, Xiaoping ; Qu, Yuting ; Yang, Mei ; Qiu, Chaoran ; Li, Weiwen ; Huang, Hui ; Liao, Chunbang ; Lin, Zhiquan ; Huang, Shengchao

BackgroundAcquired lymphedema is a common and often severe complication of breast cancer surgery and radiology that seriously affects patients' quality of life. Nevertheless, the pathogenesis for acquired lymphedema is complex and remains unclear. The aim of this study is to find out possible genetic markers and potential drugs for acquired lymphedema.MethodsFirst, the GSE4333 datasets, which include expression data for six female humanized hairless immunocompetent SKH-1 mice (the condition of whom mimics acquired lymphedema), were reanalyzed. According to the criteria of a fold change (FC) ≥1.4 and an adjusted P value <0.05, we identified the differentially expressed genes (DEGs) between a normal group and the lymphedema group. Next, we analyzed the Gene Ontology (GO) terms and enriched signaling pathways associated with these DEGs with an online tool DAVID. We also constructed protein-protein interaction (PPI) networks and selected meaningful gene modules for additional gene-drug interaction research. Finally, the extant drugs targeting these module genes were identified for further study of their therapeutic effects against acquired lymphedema.ResultsA total of 481 DEGs were identified that were closely associated with the immune system, inflammatory response, and extracellular matrix (ECM) structural constituent terms, among others. Moreover, we identified the top 10 significant genes in the PPI networks and identified one extant drug, fiboflapon, that targets the ALOX5AP gene.ConclusionsWe ultimately identified 10 hub genes, molecular mechanisms, and one extant drug related to acquired lymphedema. The findings identified targets and a potential drug for further research on acquired lymphedema.

01 Oct 2021·Prostaglandins & Other Lipid MediatorsQ3 · BIOLOGY

Intrinsic 5-lipoxygenase activity regulates migration and adherence of mantle cell lymphoma cells

Q3 · BIOLOGY

Article

Author: Claesson, Hans-Erik ; Strååt, Klas ; Björkholm, Magnus ; Wright, Anthony P ; Merrien, Magali ; Österborg, Anders ; Sander, Birgitta ; Xia, Chuanyou ; Sadeghi, Laia ; Xu, Dawei

Human B-lymphocytes express 5-lipoxygenase (5-LOX) and 5-LOX activating protein (FLAP) and can convert arachidonic acid to leukotriene B₄. Mantle cell lymphoma (MCL) cells contain similar amounts of 5-LOX as human neutrophils but the function and mechanism of activation of 5-LOX in MCL cells, and in normal B-lymphocytes, are unclear. Here we show that the intrinsic 5-LOX pathway in the MCL cell line JeKo-1 has an essential role in migration and adherence of the cells, which are important pathophysiological characteristics of B-cell lymphoma. Incubation of JeKo-1 with the FLAP inhibitor GSK2190915 or the 5-LOX inhibitor zileuton, at a concentration below 1 μM, prior to stimulation with the chemotactic agent CXCL12, led to a significant reduction of migration. CRISPR/Cas9 mediated deletion of ALOX5 gene in JeKo-1 cells also led to a significantly decreased migration of the cells. Furthermore, 5-LOX and FLAP inhibitors markedly decreased the adherence of JeKo-1 cells to stromal cells. In comparison, these drugs had a similar effect on adherence of JeKo-1 cells as the Bruton tyrosine kinase inhibitor ibrutinib, which has a proven anti-tumour effect. These results indicate that inhibition of 5-LOX may be a novel treatment for MCL and certain other B-cell lymphomas.

01 Sep 2020·Chemical Biology & Drug DesignQ4 · MEDICINE

Fingerprint‐based computational models of 5‐lipo‐oxygenase activating protein inhibitors: Activity prediction and structure clustering

Q4 · MEDICINE

Article

Author: Huo, Donghui ; Tu, Guiping ; Yan, Aixia ; Qin, Zijian ; Zhang, Shengde

AbstractInflammatory diseases can be treated by inhibiting 5‐lipo‐oxygenase activating protein (FLAP). In this study, a data set containing 2,112 FLAP inhibitors was collected. A total of 25 classification models were built by five machine learning algorithms with five different types of fingerprints. The best model, which was built by support vector machine algorithm with ECFP_4 fingerprint had an accuracy and a Matthews correlation coefficient of 0.862 and 0.722 on the test set, respectively. The predicted results were further evaluated by the application domain dSTD‐PRO (a distance between one compound to models). Each compound had a dSTD‐PRO value, which was calculated by the predicted probabilities obtained from all 25 models. The application domain results suggested that the reliability of predicted results depended mainly on the compounds themselves rather than algorithms or fingerprints. A group of customized 10‐bit fingerprint was manually defined for clustering the molecular structures of 2,112 FLAP inhibitors into eight subsets by K‐Means. According to the clustering results, most of inhibitors in two subsets (subsets 2 and 4) were highly active inhibitors. We found that aryl oxadiazole/oxazole alkanes, biaryl amino‐heteroarenes, two aromatic rings (often N‐containing) linked by a cyclobutene group, and 1,2,4‐triazole group were typical fragments in highly active inhibitors.

100 Deals associated with Fiboflapon Sodium

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D10122	-	-	DB06346

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Persistent asthma	Phase 2	Bulgaria	GSK Plc	28 Jun 2010
Persistent asthma	Phase 2	Poland	GSK Plc	28 Jun 2010
Persistent asthma	Phase 2	United States	GSK Plc	28 Jun 2010
Persistent asthma	Phase 2	Romania	GSK Plc	28 Jun 2010
Persistent asthma	Phase 2	Japan	GSK Plc	28 Jun 2010
Asthma	Phase 2	United Kingdom	GSK Plc	01 Dec 2008
Asthma	Phase 2	United Kingdom	GSK Plc	01 Dec 2008
Asthma	Phase 2	Netherlands	GSK Plc	01 Dec 2008
Asthma	Phase 2	Netherlands	GSK Plc	01 Dec 2008
Asthma, Exercise-Induced	Phase 2	United States	GSK Plc	01 Dec 2008

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00850642 (CTgov)	Phase 2	Asthma	7	Placebo	yxyibxxllx(usgzioqfuw) = ibdwcsbbbv dedwwtnizi (jicxwzddcb, fwfdtsiuzu - ajqgicbbpn) View more	-	01 Mar 2018
NCT00812929 (GSK Clinical Study LPA112025, CTgov)	Phase 2	Asthma \| Asthma, Exercise-Induced	47	Placebo (Placebo)	wzosyqyfxy(mjytqbqgcx) = tijbpstlbt uuhzaxznyx (fhjqujlajx, ezkqoureru - gugmbfwcxu) View more	-	19 Sep 2017
				GSK2190915 (GSK2190915 10 mg)	wzosyqyfxy(mjytqbqgcx) = iqnkfcchgn uuhzaxznyx (fhjqujlajx, yggekrgsxo - xuexzgennq) View more
NCT01147744 (CTgov)	Phase 2	Persistent asthma	700	placebo+montelukast (Placebo)	xpbyqyrtum(jkghzraqeh) = odnrxufxjz fytlbxhzoz (ngymfvnfxp, eagapkjuws - uwdqwqnmcs) View more	-	06 Sep 2017
				GSK2190915 (GSK2190915 10 mg)	xpbyqyrtum(jkghzraqeh) = qtgcqivobh fytlbxhzoz (ngymfvnfxp, gyxvlsopgo - agwojsauns) View more
NCT01156792 (CTgov)	Phase 2	Asthma	162	FP (FP + Placebo)	eybkihyunp(obmyhbolyg) = srzksymwgq dqwfdasogl (yvnopocava, gpilqgjdtl - ohotbywcgi) View more	-	03 Feb 2017
				FP+GSK2190915 (FP + GSK2190915 100 mg)	eybkihyunp(obmyhbolyg) = oxjbclgosd dqwfdasogl (yvnopocava, iytyfkixnz - deyyzhlrew) View more
NCT00812929 (GSK Clinical Study LPA112025, Pubmed \| Allergy Asthma Proc)	Phase 2	Asthma, Exercise-Induced	47	GSK2190915 200 mg	ibaqzghilg(ujxelukmyf) = thhimbjyik banzhlrkat (unaeadmmab, 3.06 - 9.54)	-	30 Apr 2014
NCT00748306 (Pubmed \| Clin Exp Allergy)	Phase 2	Mild asthma	19	GSK2190915 100 mg	tkxcwlutud(fqrvxccpsf) = qimenbtmhc rayrdfrcgc (bzvgxbrduh ) View more	-	01 Feb 2013
NCT00748306 (ERS2011)	Phase 2	Asthma	19	GSK2190915 100 mg	dmowtlelfq(jjjyibvuww) = ztnfvqlvmt zhwzcuaqqj (rdbhmjfjng ) View more	Positive	01 Sep 2011
				Placebo	gdlredmiqz(vxyolnkyos) = ljvucpbuml spcrvenbfi (rstmptzpuy )
NCT00812773 (ERS2011)	Phase 2	Asthma	19	GSK2190915 10mg	olykyjtyrm(tqxjwsopdl) = ucswvstric lywezklpek (tlorhurtqu )	Positive	01 Sep 2011
				GSK2190915 50mg	olykyjtyrm(tqxjwsopdl) = wzrznxcfaf lywezklpek (tlorhurtqu )
NCT00748306 (LPA111834, ERS2011)	Phase 2	Asthma cysteinyl leukotrienes (cLTs)	-	GSK2190915 100mg	pdotdqpnhx(vfjqjqaciz) = nvgumgszig hpgnccnsjd (zabqetfhkc )	-	01 Sep 2011
				Placebo	pdotdqpnhx(vfjqjqaciz) = fxuyuscxxr hpgnccnsjd (zabqetfhkc )