Mapracorat(Mapracorat) - 药物靶点：GR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Mapracorat (USAN)

+ [2]

靶点

GR

作用机制

GR激动剂(糖皮质激素受体激动剂)

治疗领域

神经系统疾病眼部疾病其他疾病+ [3]

在研适应症-

非在研适应症

白内障变应性结膜炎角膜内皮细胞损失+ [7]

原研机构

Bayer AG

在研机构-

非在研机构

Bayer AG

Bausch & Lomb, Inc.

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

结构

分子式C25H26F4N2O2

InChIKeyVJGFOYBQOIPQFY-XMMPIXPASA-N

CAS号887375-26-0

关联

16

项与 Mapracorat 相关的临床试验

NCT03399526 / Completed临床1期

A 28-day, Double-blind, Randomized, Reference-controlled Open Psoriasis Plaque Test for Within Subject Comparison of Efficacy and Safety of Mapracorat 0.1% Ointment and 4 Reference Products in Symptomatic Volunteers With Stable Plaque-type Psoriasis

Evaluation of efficacy and safety of Mapracorat 0.1% ointment and 4 comparator ointments in male and female subjects 18 to 65 years with stable plaque-type psoriasis treated once daily 6 days a week for a maximum of 4 weeks.
Primary objective was to compare the efficacy of all test compounds by measurement of psoriatic infiltrate thickness (PIT) with 20 MHz B mode ultrasound.
Secondary objectives were to assess safety of all test compounds by measurement of the atrophogenic potential on non-lesional skin with 20 MHz B mode ultrasound, to assess the efficacy of all test compounds by measurement of intensity of erythema measured by chromametry, to assess the efficacy of all test compounds by visual assessment of the skin in the test fields using a 5-point score, to assess the safety of all test compounds by visual assessments of formation of teleangiectasia using a 5-point score, to assess the safety of all test compounds by visual assessment of atrophy using a 5-point score, to assess the safety of all test compounds by visual assessment of local tolerability using a 5-point score, to visualize the therapeutic index given by PIT versus non lesional skin thickness.

开始日期2013-02-11

申办/合作机构

Bayer AG

NCT01736462 / Completed临床1期

An Open-Label Study to Evaluate 3 Month Corneal Endothelial Cell Density Changes in Healthy Subjects When Mapracorat Ophthalmic Suspension, 3%, is Administered 4 Times Daily for 14 Days

The objective of this study is to evaluate the effect on corneal endothelial cell density (cells/mm²) changes at 3 months when mapracorat ophthalmic suspension, 3% is administered QID (four times daily), for 14 days in healthy subjects with a normal ophthalmic history.

开始日期2013-02-01

申办/合作机构

Bausch & Lomb, Inc.

NCT01591655 / Completed临床3期

The Efficacy and Safety of Mapracorat Ophthalmic Suspension, 3% in Subjects for the Treatment of Ocular Inflammation and Pain Following Cataract Surgery.

The objective of this clinical study is to compare the safety and efficacy of mapracorat ophthalmic suspension, 3% with its vehicle for the treatment of postoperative inflammation and pain following cataract surgery. Participants from the United States and Canada will be recruited for this study.

开始日期2012-07-01

申办/合作机构

Bausch & Lomb, Inc.

100 项与 Mapracorat 相关的临床结果

登录后查看更多信息

100 项与 Mapracorat 相关的转化医学

登录后查看更多信息

100 项与 Mapracorat 相关的专利（医药）

登录后查看更多信息

14

项与 Mapracorat 相关的文献（医药）

2017-02-01·Veterinary Dermatology3区 · 农林科学

The selective glucocorticoid receptor agonist mapracorat displays a favourable safety–efficacy ratio for the topical treatment of inflammatory skin diseases in dogs

3区 · 农林科学

Article

作者: Schmidt, Bernard H. ; Rossbach, Kristine ; Bäumer, Wolfgang

BackgroundMapracorat is a nonsteroidal Selective Glucocorticoid Receptor Agonist (SEGRA) that is presumed to have a better therapeutic index compared to classical glucocorticoids.ObjectivesTo compare the efficacy and safety of mapracorat with classical glucocorticoids used for the treatment of allergic skin diseases in dogs.AnimalsSix laboratory beagles.MethodsThe effect of mapracorat on lipopolysaccharide‐induced TNFα secretion from canine peripheral blood derived mononuclear cells (PBMC) was tested. In vivo, mapracorat was compared to triamcinolone acetonide using a skin inflammation model. Skin fold thickness was determined after daily administration of mapracorat and triamcinolone acetonide over 14 days.ResultsMapracorat concentration dependently inhibited TNFα secretion from activated canine PBMC with a half maximal inhibitory concentration (IC50) value of approximately 0.2 nmol/L. Intradermal injection of compound 48/80 (50 μg in 50 μL saline) resulted in a clear wheal and flare reaction over the 60 min observation period. Topical pre‐treatment with mapracorat (0.1%) and triamcinolone acetonide (0.015%) led to significant reduction in the wheal and flare responses compared to vehicle (acetone) treated areas. However, once daily topical administration of triamcinolone acetonide significantly reduced skin fold thickness from day 8 to 14, whereas no such reduction was observed for mapracorat.ConclusionThese results demonstrate that mapracorat has comparable anti‐inflammatory efficacy to classical steroidal glucocorticoids under these experimental settings and maintenance of skin fold thickness indicates a better safety profile compared to triamcinolone acetonide at equipotent concentrations. This profile further suggests that SEGRAs show promise in the management of inflammatory and pruritic skin diseases in dogs.

2017-01-01·Skin Pharmacology and Physiology4区 · 医学

Comparison of Occlusive and Open Application in a Psoriasis Plaque Test Design, Exemplarily Using Investigations of Mapracorat 0.1% Ointment versus Vehicle and Reference Drugs

4区 · 医学

Article

作者: Staedtler, Gerald ; Grossmann, Ulrike ; Wigger-Alberti, Walter ; Shakery, Kaweh ; von Mackensen, Yi-Ling ; Hoffman-Wecker, Maciej ; Nkulikiyinka, Richard ; Williams, Ragna

Background/Aims: Psoriasis plaque tests (PPTs) are important tools in the early phases of antipsoriatic drug development. Two distinct PPT design variants (open vs. occluded drug application) are commonly used, but no previous work has aimed to directly compare and contrast their performance. Methods: We compared the antipsoriatic efficacy of mapracorat 0.1% ointment and reference drugs reported in 2 separate studies, representing open and occluded PPT designs. The drug effect size was measured by sonography (mean change in echo-poor band thickness), chromametry, and standardized clinical assessment. Results: Antipsoriatic effects were detectable for the study drugs in both occluded and open PPTs. Differences between the potency of antipsoriatic drugs and vehicle were observable. The total antipsoriatic effect size appeared to be higher in the occluded PPT than the open PPT, despite the shorter treatment duration (2 vs. 4 weeks). Effect dynamics over time revealed greater differences between some study drugs in the open PPT compared to the occluded PPT. Conclusion: Taking the higher technical challenges for the open PPT into account, we recommend the occluded PPT as a standard screening setting in early drug development. In special cases, considering certain drug aspects or study objectives that would require procedural adaptations, an open PPT could be the better-suited design. Finally, both PPT models show clear advantages: classification as phase I studies, small number of psoriatic subjects, relatively short study duration, excellent discrimination between compounds and concentrations, parallel measurement of treatment response, and go/no go decisions very early in clinical development.

2015-01-29·Inflammation & Allergy-Drug Targets

Mapracorat, a Novel Non-Steroidal Selective Glucocorticoid Receptor Agonist for the Treatment of Allergic Conjunctivitis

Review

作者: Baiula, Monica ; Spampinato, Santi

Glucocorticoids are used to treat chronic and severe forms of allergic conjunctivitis. Although they exert a rapid and powerful therapeutic activity, relevant side effects may limit their ocular use: increase of intraocular pressure, cataract formation and reduced resistance to infections. New glucocorticoids displaying the same potency of classical glucocorticoids but with fewer adverse effects are needed for the treatment of ocular disorders. Mapracorat (also known as ZK245186 or BOL-303242-X) is a novel non-steroidal selective glucocorticoid receptor agonist that is in the first phases of clinical evaluation (Phase II Clinical trials) for topical treatment of inflammatory skin and ocular disorders. Mapracorat binds selectively to human glucocorticoid receptor and displays powerful anti-inflammatory effects. In experimental models of ocular diseases, mapracorat reduces clinical symptoms, eosinophil recruitment, chemokines and pro-inflammatory cytokines production at ocular level, confirming that it acts preventing both the early and late phase of allergic response. Interestingly, mapracorat induces a lower increase of intraocular pressure in comparison to the classical glucocorticoid dexamethasone. Several clinical trials are ongoing to investigate the efficacy and safety of mapracorat for the treatment of several ocular diseases. Transrepressive mechanisms are thought to account for the majority of mapracorat's antiinflammatory effects; however, the induction of anti-inflammatory proteins likely involved in transactivation events may contribute to mapracorat-mediated anti-inflammatory properties and deserve to be further investigated in suitable in vivo and in vitro models. These observations may influence how novel "differential" ligands are discovered, identified and evaluated.

100 项与 Mapracorat 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D10136	Mapracorat	-	DB12041

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
斑块状银屑病	临床3期	德国	Bayer AG	2013-02-11
角膜内皮细胞损失	临床3期	美国	Bausch & Lomb, Inc.	2013-02-01
眼科外科手术	临床3期	美国	Bausch & Lomb, Inc.	2012-07-01
湿疹	临床3期	德国	Bayer AG	2011-05-01
变应性结膜炎	临床3期	美国	Bausch & Lomb, Inc.	2011-02-01
疼痛	临床3期	美国	Bausch & Lomb, Inc.	2011-02-01
白内障	临床3期	美国	Bausch & Lomb, Inc.	2010-11-01
眼部炎症	临床3期	美国	Bausch & Lomb, Inc.	2010-11-01
干眼综合征	临床3期	美国	Bausch & Lomb, Inc.	2010-07-01
特应性皮炎	临床3期	南非	Bayer AG	2009-07-15

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01289431 (CTgov)	临床2期	变应性结膜炎	236	BOL-303242-X (0.3% Once a Day)	蓋積鏇艱餘積憲鹽膚夢(鏇觸鏇顧獵願餘範夢製) = 襯製網鑰憲鹹鹹淵構製鹹遞鹹鬱壓艱鹽窪憲夢 (構顧遞積壓製網簾簾齋, 築鬱蓋襯簾鹹鏇醖製壓 ~ 夢鬱選餘齋憲鹹鏇鑰鹹) 更多	-	2020-09-04
				BOL-303242-X (2% Once a Day)	蓋積鏇艱餘積憲鹽膚夢(鏇觸鏇顧獵願餘範夢製) = 築壓鬱糧繭壓衊遞膚夢鹹遞鹹鬱壓艱鹽窪憲夢 (構顧遞積壓製網簾簾齋, 遞廠衊鬱淵製鏇選廠襯 ~ 遞遞積淵醖網蓋廠衊願) 更多
NCT01591161 (CTgov)	临床3期	白内障 \| 疼痛 \| 眼部炎症 \| 眼科外科手术	369	Mapracorat (Mapracorat)	獵鏇壓餘鑰廠獵餘餘醖(餘網夢夢淵繭觸膚遞選) = 選淵鬱鹽醖構網遞齋蓋壓構壓構糧艱願顧鑰鹽 (顧鬱醖積繭選憲遞鑰遞, 築觸膚獵餘鹽廠蓋鹹網 ~ 鏇糧鏇簾窪製窪範蓋膚) 更多	-	2020-09-03
				Placebo (Vehicle)	獵鏇壓餘鑰廠獵餘餘醖(餘網夢夢淵繭觸膚遞選) = 鬱鹽鹽齋壓夢願觸鏇構壓構壓構糧艱願顧鑰鹽 (顧鬱醖積繭選憲遞鑰遞, 夢簾淵製襯夢築鹽遞衊 ~ 簾遞築遞築醖壓鑰獵簾) 更多
NCT01163643 (CTgov)	临床2期	干眼综合征	356	2% BOL-303242-X ophthalmic suspension (2% BOL-303242-X Ophthalmic Suspension)	壓構構繭簾繭範艱窪餘(糧築膚網窪艱膚繭獵觸) = 襯糧醖顧範夢簾鏇憲鹹網憲築糧鏇糧鑰廠壓艱 (襯廠鏇積遞繭膚餘獵壓, 遞鏇鏇繭壓範鹽夢觸願 ~ 醖糧鹹製糧鏇憲顧鏇鹽) 更多	-	2020-09-03
				2% BOL-303242-X ophthalmic suspension AM (2% BOL-303242-X Ophthalmic Suspension in the Morning)	壓構構繭簾繭範艱窪餘(糧築膚網窪艱膚繭獵觸) = 鹽範醖選繭餘鬱餘顧醖網憲築糧鏇糧鑰廠壓艱 (襯廠鏇積遞繭膚餘獵壓, 鹹蓋選齋艱膚夢襯觸淵 ~ 範淵選膚鏇衊醖獵艱繭) 更多
NCT01591655 (CTgov)	临床3期	白内障 \| 疼痛 \| 眼部炎症 \| 眼科外科手术	360	Mapracorat (Mapracorat)	醖齋壓鏇構衊壓顧齋蓋(膚襯廠築窪窪憲醖廠壓) = 顧廠鬱蓋願鏇製鑰鬱願築積構鹹醖鏇積壓餘夢 (窪構襯壓衊網積艱夢簾, 獵獵鏇淵選製糧蓋網鑰 ~ 淵鏇簾窪遞齋築艱齋鹽) 更多	-	2020-09-03
				Vehicle (Vehicle)	醖齋壓鏇構衊壓顧齋蓋(膚襯廠築窪窪憲醖廠壓) = 鏇鏇蓋鏇顧顧繭觸網壓築積構鹹醖鏇積壓餘夢 (窪構襯壓衊網積艱夢簾, 蓋築夢繭繭簾製獵遞鏇 ~ 淵淵繭鬱願積夢選願艱) 更多
NCT01230125 (CTgov)	临床3期	白内障 \| 眼部炎症	311	Mapracorat (Mapracorat)	觸遞簾憲鹽齋鑰製製夢(餘觸憲顧築衊鬱網憲淵) = 淵範壓壓遞構衊醖築憲顧遞遞繭繭夢繭淵積網 (窪膚積網淵淵鏇鬱鬱積, 顧網繭鏇顧廠簾築鑰餘 ~ 構獵築繭觸醖醖淵顧淵) 更多	-	2020-09-03
				Vehicle (Vehicle)	觸遞簾憲鹽齋鑰製製夢(餘觸憲顧築衊鬱網憲淵) = 鹹簾選鹹製構廠鏇夢鏇顧遞遞繭繭夢繭淵積網 (窪膚積網淵淵鏇鬱鬱積, 憲遞獵廠夢鹽淵築鏇餘 ~ 衊範製鑰艱簾夢艱艱艱) 更多
NCT01298752 (CTgov)	临床3期	白内障 \| 疼痛 \| 眼部炎症	177	Mapracorat (Mapracorat)	廠構淵觸襯製艱繭願網(選衊蓋選膚廠憲鏇顧網) = 鏇鹽壓夢夢觸蓋憲製鬱膚顧簾製鑰鹽壓選選齋 (鑰製網獵製糧醖網齋壓, 築鹹遞鏇獵膚夢鑰餘構 ~ 鹹獵糧膚鑰壓網醖餘鑰) 更多	-	2020-09-03
				Vehicle (Vehicle)	廠構淵觸襯製艱繭願網(選衊蓋選膚廠憲鏇顧網) = 壓壓糧積餘獵獵顧齋築膚顧簾製鑰鹽壓選選齋 (鑰製網獵製糧醖網齋壓, 壓鹽淵鬱繭簾製製艱積 ~ 鹽壓襯艱餘餘鏇夢憲鏇) 更多
NCT00905450 (CTgov)	临床2期	白内障 \| 炎症	415	Vehicle for BOL-303242-X	憲鏇製遞獵廠願襯願壓(衊鏇壓積網願衊窪夢製) = 蓋鑰壓觸觸夢鏇鹹顧鬱夢鹹繭齋獵願選衊鏇製 (顧衊鹹廠鹽願憲鬱網蓋, 膚範窪製淵網蓋構淵齋 ~ 襯願廠壓鹽鑰遞壓壓範) 更多	-	2020-09-03
ARVO2010	N/A	-	-	BOL-303242-X	(膚窪觸積鹹顧淵廠襯獵) = 製簾範選製鏇願醖壓餘積遞廠築糧鏇簾醖蓋獵 (鏇膚鬱範淵醖築夢繭齋 )	-	2010-04-01
BOL-303242-X (ARVO2010)	N/A	-	-	BOL-303242-X	(製齋製繭壓廠鑰遞獵憲) = 繭範夢選淵齋餘蓋蓋選簾齋鏇選襯夢選鑰糧衊 (衊網鏇艱窪餘鹹憲鑰鹹 )	-	2010-04-01
				Dexamethasone	(製齋製繭壓廠鑰遞獵憲) = 淵鏇願艱製衊顧鬱顧繭簾齋鏇選襯夢選鑰糧衊 (衊網鏇艱窪餘鹹憲鑰鹹 )