Delving into the Latest Updates on Gemilukast with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

CysLT1 antagonists(Cysteinyl leukotriene receptor 1 antagonists), CysLT2 antagonists(cysteinyl leukotriene receptor 2 antagonists)

Therapeutic Areas

Immune System DiseasesRespiratory DiseasesOther Diseases

Active Indication-

Inactive Indication

AsthmaAsthma, Exercise-Induced

Originator Organization

Ono Pharmaceutical Co., Ltd.

Active Organization-

Inactive Organization

Ono Pharma USA, Inc.

Ono Pharmaceutical Co., Ltd.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC36H37F2NO5

InChIKeySILHYVDKGHXGBL-UHFFFAOYSA-N

CAS Registry1232861-58-3

The primary objectives are
to determine the effect of ONO-6950 200 mg QD versus placebo administered for 8 days on early asthmatic response (EAR) and late asthmatic response (LAR) induced by inhaled allergen
to determine the safety and tolerability of ONO-6950 200 mg QD administered for 8 days in patients with asthma
The secondary objectives are:
to compare the effect of ONO-6950 versus montelukast on the % decrease of FEV1 following allergen exposure, and
to determine the effect of ONO-6950 versus placebo and montelukast on allergen-induced airway hyperresponsiveness (AHR) as measured by methacholine challenge

Start Date01 Jun 2012

Sponsor / Collaborator

Ono Pharma USA, Inc.

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100 Clinical Results associated with Gemilukast

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100 Translational Medicine associated with Gemilukast

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100 Patents (Medical) associated with Gemilukast

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4

Literatures (Medical) associated with Gemilukast

01 Dec 2016·AllergyQ1 · MEDICINE

A dual CysLT_1/2 antagonist attenuates allergen‐induced airway responses in subjects with mild allergic asthma

Q1 · MEDICINE

Article

Author: FitzGerald, J. M. ; Davis, B. E. ; Tanaka, M. ; Cockcroft, D. W. ; Boulet, L.-P. ; Gauvreau, G. M. ; Fourre, J. A. ; Leigh, R. ; Nabata, T. ; O'Byrne, P. M. ; Tanaka, M.

AbstractBackgroundThe cysteinyl leukotrienes (cysLTs) play a key role in the pathophysiology of asthma. In addition to functioning as potent bronchoconstrictors, cysLTs contribute to airway inflammation through eosinophil and neutrophil chemotaxis, plasma exudation, and mucus secretion. We tested the activity of the dual cysLT1/2 antagonist, ONO‐6950, against allergen‐induced airway responses.MethodsSubjects with documented allergen‐induced early (EAR) and late asthmatic response (LAR) were randomized in a three‐way crossover study to receive ONO‐6950 (200 mg) or montelukast (10 mg) or placebo q.d. on days 1–8 of the three treatment periods. Allergen was inhaled on day 7 two hours postdose, and forced expiratory volume in 1 s (FEV1) was measured for 7 h following challenge. Sputum eosinophils and airway hyperresponsiveness were measured before and after allergen challenge. The primary outcome was the effect of ONO‐6950 vs placebo on the EAR and LAR.ResultsTwenty‐five nonsmoking subjects with mild allergic asthma were enrolled and 20 subjects completed all three treatment periods per protocol. ONO‐6950 was well tolerated. Compared to placebo, ONO‐6950 significantly attenuated the maximum % fall in FEV1 and area under the %FEV1/time curve during the EAR and LAR asthmatic responses (P < 0.05) and allergen‐induced sputum eosinophils. There were no significant differences between ONO‐6950 and montelukast.ConclusionsAttenuation of EAR, LAR, and airway inflammation is consistent with cysLT1 blockade. Whether dual cysLT1/2 antagonism offers additional benefit for treatment of asthma requires further study.

01 Oct 2015·European Journal of PharmacologyQ3 · MEDICINE

Effects of ONO-6950, a novel dual cysteinyl leukotriene 1 and 2 receptors antagonist, in a guinea pig model of asthma

Q3 · MEDICINE

Article

Author: Murata, Masayuki ; Yonetomi, Yasuo ; Sekioka, Tomohiko ; Kamiya, Akihiro ; inoue, Atsuto ; Nakao, Takafumi ; Kadode, Michiaki ; Kitamine, Tetsuya ; Nakao, Shintaro ; Nomura, Hiroaki ; Nakade, Shinji ; Fujita, Manabu ; Nambu, Fumio ; Kawabata, Kazuhito

We assessed in this study the anti-asthmatic effects of ONO-6950, a novel cysteinyl leukotriene 1 (CysLT1) and 2 (CysLT2) receptors dual antagonist, in normal and S-hexyl glutathione (S-hexyl GSH)-treated guinea pigs, and compared these effects to those of montelukast, a CysLT1 selective receptor antagonist. Treatment with S-hexyl GSH reduced animals LTC4 metabolism, allowing practical evaluation of CysLT2 receptor-mediated airway response. ONO-6950 antagonized intracellular calcium signaling via human and guinea pig CysLT1 and CysLT2 receptors with IC50 values of 1.7 and 25 nM, respectively (human receptors) and 6.3 and 8.2 nM, respectively (guinea pig receptors). In normal guinea pigs, both ONO-6950 (1 or 0.3 mg/kg, p.o.) and the CysLT1 receptor antagonist montelukast (0.3 or 0.1 mg/kg, p.o.) fully attenuated CysLT1-mediated bronchoconstriction and airway vascular hyperpermeability induced by LTD4. On the other hand, in S-hexyl GSH-treated guinea pigs ONO-6950 at 3 mg/kg, p.o. or more almost completely inhibited bronchoconstriction and airway vascular hyperpermeability elicited by LTC4, while montelukast showed only partial or negligible inhibition of these airway responses. In ovalbumin sensitized guinea pigs, treatment with S-hexyl GSH on top of pyrilamine and indomethacin rendered antigen-induced bronchoconstriction sensitive to both CysLT1 and CysLT2 receptor antagonists. ONO-6950 strongly inhibited this asthmatic response to the level attained by combination therapy with montelukast and BayCysLT2RA, a selective CysLT2 receptor antagonist. These results clearly demonstrate that ONO-6950 is an orally active dual CysLT1/LT2 receptor antagonist that may provide a novel therapeutic option for patients with asthma.

01 Oct 2015·Allergology InternationalQ2 · MEDICINE

Expression of CysLT2 receptors in asthma lung, and their possible role in bronchoconstriction

Q2 · MEDICINE

ArticleOA

Author: Takashi Abe ; Masanori Fujii ; Shigekatsu Kohno ; Tomohiko Sekioka ; Michiaki Kadode ; Kazuhito Kawabata ; Takeshi Nabe ; Michiaki Horiba

BACKGROUNDThe expression and functional role of CysLT2 receptors in asthma have not been clarified. In this study, we evaluated CysLT2 receptors expression, and effects of CysLT2-and CysLT1/2-receptor antagonists on antigen-induced bronchoconstriction using isolated lung tissues from both asthma and non-asthma subjects.METHODSCysLT1 and CysLT2 receptors expression in asthma and non-asthma lung tissue preparations was examined in immunohistochemistry experiments, and their functional roles in antigen-induced bronchoconstriction were assessed using ONO-6950, a dual CysLT1/2-receptor antagonist, montelukast, a CysLT1 receptor antagonist, and BayCysLT2RA, a CysLT2 receptor-specific antagonist.RESULTSCysLT1 receptors were expressed on the bronchial smooth muscle and epithelium, and on alveolar leukocytes in 5 in 5 non-asthma subjects and 2 in 2 asthma subjects. On the other hand, although degrees of CysLT2 receptors expression were variable among the 5 non-asthma subjects, the expression in the asthma lung was detected on bronchial smooth muscle, epithelium and alveolar leukocytes in 2 in 2 asthma subjects. In the non-asthma specimens, antagonism of CysLT2 receptors did not affect antigen-induced bronchial contractions, even after pretreatment with the CysLT1-receptor specific antagonist, montelukast. However, in the bronchus isolated from one of the 2 asthma subjects, antagonism of CysLT2 receptors suppressed contractions, and dual antagonism of CysLT1 and CysLT2 receptors resulted in additive inhibitory effect on anaphylactic contractions.CONCLUSIONSCysLT2 receptors were expressed in lung specimens isolated from asthma subjects. Activation of CysLT2 receptors may contribute to antigen-induced bronchoconstriction in certain asthma population.

100 Deals associated with Gemilukast

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