MK-0873(MK-0873) - 药物靶点：PDE4_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PDE4

作用机制

PDE4抑制剂(磷酸二酯酶4抑制剂)

治疗领域

免疫系统疾病呼吸系统疾病皮肤和肌肉骨骼疾病

在研适应症-

非在研适应症

斑块状银屑病慢性阻塞性肺疾病类风湿关节炎

原研机构

Merck Sharp & Dohme Corp.

在研机构-

非在研机构

Merck GmbH

Merck Sharp & Dohme Corp.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C25H18N4O3

InChIKeyJJWKQXNHYDJXKF-UHFFFAOYSA-N

CAS号500355-52-2

关联

4

项与 MK-0873 相关的临床试验

NCT01235728 / Completed临床1期

A Double Blind, Active-Comparator-, and Vehicle-Controlled, Multiple-Dose Study to Evaluate the Efficacy and Pharmacokinetics of MK-0873 in Patients With Plaque Psoriasis

This is a within-participant comparison study to investigate the efficacy of a 28-day regimen of MK-0873 2% cream twice a day (b.i.d.) compared to MK-0873 vehicle (matching placebo) b.i.d. as well as to a positive control comparator calcitriol 0.0003% (3 µg/g) in participants with plaque psoriasis. In order to be enrolled in the study, patients need to have at least two pairs (lesions AB and CD) of approximately similar plaque lesions in severity and size of surface area involved and located in approximately symmetric regions such as the trunk or limbs of the body. Participants will be randomly assigned to apply either MK-0873 or MK-0873 vehicle to plaque A or B and will be randomly assigned to apply MK-0873 or calcitriol to plaque C or D. It is hypothesized that MK-0873 cream formulation administered to participants with psoriasis by the topical route will result in a statistically greater percent target lesion severity (TLS) reduction in plaque lesion than will MK-0873 Vehicle on Day 29.

开始日期2010-11-01

申办/合作机构

Merck Sharp & Dohme Corp.

NCT01140061 / Completed临床1期

A 3-Part Study to Evaluate Safety, Tolerability, and Pharmacokinetics of MK-0873 Following Cumulative Patch and Repeated Max Area Applications in Healthy Subjects and Psoriasis Patients

This study will evaluate the incidence of erythema and other local cutaneous irritation after administration of MK-0873 by patch or cream formulation in healthy participants and participants with mild psoriasis. Part I and Part II in healthy participants will be initiated prior to Part III in psoriasis participants. The primary hypotheses of the study are: 1) that MK-0873 is safe and well tolerated in healthy participants and participants with psoriasis and 2) that the maximum plasma concentration of MK-0873 is <20 nM in healthy participants and participants with psoriasis.

开始日期2010-05-01

申办/合作机构

Merck Sharp & Dohme Corp.

NCT00132769 / Completed临床2期

A Randomized, Placebo-Controlled, Parallel-Group, Double-Blind, 12-Week Study to Assess the Clinical Efficacy, Safety, and Tolerability of MK-0873 in Rheumatoid Arthritis

This study will look at whether this new drug is effective in the treatment of rheumatoid arthritis, and at whether it is safe and well-tolerated by participants with the disease.

开始日期2005-01-01

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 MK-0873 相关的临床结果

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100 项与 MK-0873 相关的转化医学

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100 项与 MK-0873 相关的专利（医药）

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3

项与 MK-0873 相关的文献（医药）

2015-05-01·Journal of Pharmaceutical Sciences3区 · 医学

Use of Minipig Skin Biopsy Model as an Innovative Tool to Design Topical Formulation to Achieve Desired Pharmacokinetics in Humans

3区 · 医学

Article

作者: Daniel Tatosian ; Brad Roadcap ; Lan Jin ; Christine Mestre ; Amitava Mitra ; Kimberly Manser ; Aquiles Leyes ; Naoto Uemura

In vitro cadaver skin permeation studies are often conducted to characterize the permeation profile of compounds for dermal delivery. However, its utility could be limited in the case of topical products because of lack of reliable prediction of in vivo skin kinetics. In this paper, the use of in vivo skin biopsy data to guide topical formulation development is described. A formulation was developed by compounding MK-0873, a phosphodiesterase 4 (PDE4) inhibitor, into a commercially available cream base. The cream was characterized by skin pharmacokinetic studies in minipigs, which demonstrated that MK-0873 concentrations in the epidermis and dermis were substantially higher than the IC80 for human whole blood PDE4 inhibition of ∼200 nM, suggesting that cream should provide sufficient skin exposure to assess clinical efficacy. In toxicological studies, after 1 month repeat application in minipigs minor dermal irritation and minimal systemic exposure were observed. Based on these preclinical data, the cream formulation was chosen for single rising dose clinical studies, where plasma levels of MK-0873 were mostly below the LOQ, whereas skin biopsy concentrations ranged from 6.5 to 25.1 μM. These data suggested that minipig skin biopsy model can be a valuable tool to assess performance of topical formulations and guide formulation development.

2008-10-01·Bioorganic & Medicinal Chemistry Letters4区 · 医学

Optimization and structure–activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: Identification of MK-0873, a potent and effective PDE4 inhibitor

4区 · 医学

Article

作者: Pon, Doug ; Styhler, Angela ; Huang, Zheng ; Laliberte, Sebastien ; Hamel, Pierre ; Muise, Eric ; Friesen, Richard W. ; Guay, Daniel ; Laliberte, France ; Boulet, Louise ; Girard, Mario ; Mancini, Joseph A.

A SAR study of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides is described. Optimization of the series was based on in vitro potency against PDE4, inhibition of the LPS-induced production of TNF-alpha in human whole blood and minimizing affinity for the hERG potassium channel. From these studies, compounds 18 and 20 (MK-0873) were identified as optimized PDE4 inhibitors with good overall in vitro and in vivo profiles and selected as development candidates.

2008-06-01·Pulmonary Pharmacology & Therapeutics3区 · 医学

MK-0873, a PDE4 inhibitor, does not influence the pharmacokinetics of theophylline in healthy male volunteers

3区 · 医学

Article

作者: J.M.A. Van Gerven ; M. De Smet ; M.B.A. Van Doorn ; R.C. Schoemaker ; S.L. De Haas ; D. Miller ; A.F. Cohen ; J. Wagner ; A. Denker ; Z. Diamant ; J.D. Boot ; T. Leathem

BACKGROUNDMK-0873 is a novel selective phosphodiesterase-4 inhibitor, which has been in development for the treatment of chronic obstructive pulmonary disease (COPD). In this indication, theophylline is still an important treatment, despite its relatively small therapeutic window. In view of this, it is important to investigate whether MK-0873 could affect the pharmacokinetics, safety and tolerability of theophylline, when both drugs are given concomitantly.AIMThe objective of this study was to investigate the effect of multiple doses of oral MK-0873, a selective phosphodiesterase-4 inhibitor, on the pharmacokinetics, safety and tolerability profile of orally administered theophylline in healthy volunteers.METHODSEight healthy, non-smoking male subjects participated in this randomized, open-label, 2-period, cross-over study. In one period subjects received an oral dose of 2.5mg MK-0873 for 6 days co-administered with a single oral dose of 250 mg theophylline on day 5. The other period consisted of a single dose of 250 mg theophylline on day 1. In each period, blood samples were collected at predefined time points to evaluate theophylline pharmacokinetics.RESULTSAll subjects completed the study. The study medications were generally well tolerated and no clinically relevant changes were observed in either treatment periods. No significant difference was found in the AUC 0-infinity (77.7 vs. 83.8h ng/ml; p=0.280) and Cmax (6.70 vs. 7.77 ng/ml; p=0.125) of theophylline between the MK-0873+theophylline and theophylline only treatment, and bioequivalence was demonstrated for AUC0-infinity (geometric mean ratio with 90% confidence interval: 0.930 (0.826, 1.047)).CONCLUSIONIn this study, in a limited number of subjects, co-administration of oral MK-0873 did not affect the pharmacokinetics, safety, and tolerability of oral theophylline in non-smoking healthy male subjects.

100 项与 MK-0873 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB13029

研发状态

10 条进展最快的记录,

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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2期	-	Merck Sharp & Dohme Corp.	2010-05-01
慢性阻塞性肺疾病	临床2期	哥伦比亚	Merck GmbH	-
类风湿关节炎	临床2期	加拿大	Merck GmbH	-
类风湿关节炎	临床2期	加拿大	Merck GmbH	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00132769 (CTgov)	临床2期	类风湿关节炎	106	MK-0873 (MK-0873)	網廠鏇簾網範衊壓築鏇(膚鏇憲選範鑰淵製網獵) = 糧獵膚築夢憲膚築襯蓋窪鑰艱簾襯積鹽餘壓淵 (構齋夢醖遞構繭簾鑰積, 獵製範鬱窪願醖淵簾糧 ~ 鹹衊膚淵鏇壓淵願築襯) 更多	-	2014-02-03
				Comparator: Placebo (Placebo)	網廠鏇簾網範衊壓築鏇(膚鏇憲選範鑰淵製網獵) = 糧獵製糧繭鹹鏇構衊繭窪鑰艱簾襯積鹽餘壓淵 (構齋夢醖遞構繭簾鑰積, 願繭觸齋鹹窪選窪鏇醖 ~ 廠鹽襯構積糧網鑰顧鏇) 更多