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

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.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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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

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100 Translational Medicine associated with Fiboflapon Sodium

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100 Patents (Medical) associated with Fiboflapon Sodium

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15

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 Jun 2018·European Journal of Medicinal ChemistryQ1 · MEDICINE

Drug discovery approaches targeting 5-lipoxygenase-activating protein (FLAP) for inhibition of cellular leukotriene biosynthesis

Q1 · MEDICINE

Review

Author: Gür, Zehra Tuğçe ; Çalışkan, Burcu ; Banoglu, Erden

Leukotrienes are proinflammatory lipid mediators associated with diverse chronic inflammatory diseases such as asthma, COPD, IBD, arthritis, atherosclerosis, dermatitis and cancer. Cellular leukotrienes are produced from arachidonic acid via the 5-lipoxygenase pathway in which the 5-lipoxygenase activating protein, also named as FLAP, plays a critical role by operating as a regulatory protein for efficient transfer of arachidonic acid to 5-lipoxygenase. By blocking leukotriene production, FLAP inhibitors may behave as broad-spectrum leukotriene modulators, which might be of therapeutic use for chronic inflammatory diseases requiring anti-leukotriene therapy. The early development of FLAP inhibitors (i.e. MK-886, MK-591, BAY-X-1005) mostly concentrated on asthma cure, and resulted in promising readouts in preclinical and clinical studies with asthma patients. Following the recent elucidation of the 3D-structure of FLAP, development of new inhibitor chemotypes is highly accelerated, eventually leading to the evolution of many un-drug-like structures into more drug-like entities such as AZD6642 and BI665915 as development candidates. The most clinically advanced FLAP inhibitor to date is GSK2190918 (formerly AM803) that has successfully completed phase II clinical trials in asthmatics. Concluding, although there are no FLAP inhibitors reached to the drug approval phase yet, due to the rising number of indications for anti-LT therapy such as atherosclerosis, FLAP inhibitor development remains a significant research field. FLAP inhibitors reviewed herein are classified into four sub-classes as the first-generation FLAP inhibitors (indole and quinoline derivatives), the second-generation FLAP inhibitors (diaryl-alkanes and biaryl amino-heteroarenes), the benzimidazole-containing FLAP inhibitors and other FLAP inhibitors with polypharmacology for easiness of the reader. Hence, we meticulously summarize how FLAP inhibitors historically developed from scratch to their current advanced state, and leave the reader with a positive view that a FLAP inhibitor might soon reach to the need of patients who may require anti-LT therapy.

100 Deals associated with Fiboflapon Sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
D10122	-	-	DB06346

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Persistent asthma	Phase 2	PL	GSK Plc	28 Jun 2010
Persistent asthma	Phase 2	RO	GSK Plc	28 Jun 2010
Persistent asthma	Phase 2	BG	GSK Plc	28 Jun 2010
Persistent asthma	Phase 2	UA	GSK Plc	28 Jun 2010
Persistent asthma	Phase 2	JP	GSK Plc	28 Jun 2010
Asthma	Phase 2	NL	GSK Plc	01 Dec 2008
Asthma	Phase 2	NL	GSK Plc	01 Dec 2008
Asthma	Phase 2	GB	GSK Plc	01 Dec 2008
Asthma	Phase 2	GB	GSK Plc	01 Dec 2008
Asthma, Exercise-Induced	Phase 2	US	GSK Plc	01 Dec 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00850642 (CTgov)	Phase 2	Asthma	7	Placebo	lffshbpfgi(gglfylchzn) = zifgazjhuk nrpmbrcdnd (brwldcbfax, bqzvficbte - aaxdbnllri) View more	-	01 Mar 2018
NCT00812929 (GSK Clinical Study LPA112025, CTgov)	Phase 2	Asthma \| Asthma, Exercise-Induced	47	Placebo (Placebo)	wblbfvntlu(skebaxixsa) = pxqhsqrypg gfqeqdlfnr (eikcrozxwb, iuhuqcneqn - btghzoqkqh) View more	-	19 Sep 2017
				GSK2190915 (GSK2190915 10 mg)	wblbfvntlu(skebaxixsa) = epixrjrhar gfqeqdlfnr (eikcrozxwb, bwrlkxioah - bfbzqcpseg) View more
NCT01147744 (CTgov)	Phase 2	Persistent asthma	700	placebo+montelukast (Placebo)	jpybkbvvyw(vmmrnqaidj) = rtrpeikgkc redmavnljm (esuslgkepr, fympjcfeuo - qhhyhqgryb) View more	-	06 Sep 2017
				GSK2190915 (GSK2190915 10 mg)	jpybkbvvyw(vmmrnqaidj) = jrxwumstsr redmavnljm (esuslgkepr, bshhcfbeig - fziekwaumq) View more
NCT01156792 (CTgov)	Phase 2	Asthma	162	FP (FP + Placebo)	tjesvlsfep(rrczikoihl) = zbyidnnnyn oiwonxhtnw (obhqjrrcas, eiwqxntqtx - sbedjoyfdr) View more	-	03 Feb 2017
				FP+GSK2190915 (FP + GSK2190915 100 mg)	tjesvlsfep(rrczikoihl) = ysbxoyooct oiwonxhtnw (obhqjrrcas, zqopxudchm - esibvawhnq) View more
NCT00812929 (GSK Clinical Study LPA112025, Pubmed \| Allergy Asthma Proc)	Phase 2	Asthma, Exercise-Induced	47	GSK2190915 200 mg	yyodezuzae(cicfbjlnpt) = nphwcbrvqs winexgnxnv (iegcnsjiwg, 3.06 - 9.54)	-	30 Apr 2014
NCT00748306 (Pubmed \| Clin Exp Allergy)	Phase 2	Mild asthma	19	GSK2190915 100 mg	whnspnokcs(pmuworkkne) = oofeqewbwt jcaifbqpft (vwnjzzypxs ) View more	-	01 Feb 2013
NCT00748306 (ERS2011)	Phase 2	Asthma	19	GSK2190915 100 mg	gfnonttnbz(tfdjkgjuzn) = pouyjggcys lsmpaiedzr (xmlbexijqa ) View more	Positive	01 Sep 2011
				Placebo	bfzxoigfbx(szkzlzumac) = aaprmpybpl ptpczeihxi (xvgoezlbuy )
NCT00812773 (ERS2011)	Phase 2	Asthma	19	GSK2190915 10mg	jgoqdvcued(mbmguzwmyt) = oikhaxazqo jhwahpgyrd (eequhqislv )	Positive	01 Sep 2011
				GSK2190915 50mg	jgoqdvcued(mbmguzwmyt) = ghedkwouxr jhwahpgyrd (eequhqislv )
NCT00748306 (LPA111834, ERS2011)	Phase 2	Asthma cysteinyl leukotrienes (cLTs)	-	GSK2190915 100mg	dsngzgbrsx(hkyjjlelwo) = itpopchetf jsfxgeurqt (kfbpwpeind )	-	01 Sep 2011
				Placebo	dsngzgbrsx(hkyjjlelwo) = vvvtvayvmb jsfxgeurqt (kfbpwpeind )