(MK-0773) - 药物靶点：AR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

AR

作用机制

AR调节剂(雄激素受体调节剂)

治疗领域

神经系统疾病内分泌与代谢疾病皮肤和肌肉骨骼疾病

在研适应症-

非在研适应症

肌肉萎缩骨质疏松症肌肉减少症

原研机构

Merck & Co., Inc.

在研机构-

非在研机构

Merck GmbH

Merck Sharp & Dohme Corp.

Merck & Co., Inc.

+ [1]

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-

结构

分子式C27H34FN5O2

InChIKeyGBEUKTWTUSPHEE-JWJWXJQQSA-N

CAS号606101-58-0

关联

5

项与 MK-0773 相关的临床试验

NCT00529659 / Completed临床2期

A Phase IIa Randomized, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of MK-0773 in Patients With Sarcopenia

A study to evaluate the safety, tolerability, and efficacy of MK-0773 in women with sarcopenia (loss of muscle mass).

开始日期2007-10-01

申办/合作机构

Merck Sharp & Dohme Corp.

EUCTR2007-002383-95-DK / Not yet recruitingN/A

A Phase IIa Randomized, Placebo-Controlled Clinical Trial toStudy the Efficacy and Safety of MK-0773 in Patients withSarcopenia - Sarcopenia Study

开始日期2007-08-08

申办/合作机构

Merck & Co., Inc.

NCT01017458 / Completed临床1期

A Randomized, Double-Blind, Placebo-Controlled, Double-Dummy, Multiple-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Endpoints of MK0773 in Healthy Older Men

This study will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of MK0773 in healthy older men.

开始日期2007-06-01

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 MK-0773 相关的临床结果

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100 项与 MK-0773 相关的转化医学

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100 项与 MK-0773 相关的专利（医药）

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7

项与 MK-0773 相关的文献（医药）

2021-12-01·Journal of Chromatography B3区 · 医学

Development and validation of SARMs and metabolic modulators screening in hair using UHPLC-MS/MS: Application to a doping case and first identification of S23 in authentic human hair

3区 · 医学

Article

作者: Raul, Jean-Sébastien ; Gheddar, Laurie ; Kintz, Pascal

Selective Androgen Receptors Modulators (SARMs) are a new class of doping drugs that emerged in sport since 2008. Easy access on the Internet also leads to their misuse by amateurs. It seems important for a laboratory of toxicology to develop a targeted screening of SARMs, given their health risks. A method has been developed and validated for the analysis in hair of 9 SARMs (AC262536, ACP-105, andarine, LGD-4033, MK-0773, MK 677, ostarine, RAD 410 and S23) and 2 other metabolic modulators (GW501516, SR9009), using liquid chromatography coupled to tandem mass spectrometry. After addition of bicalutamide-D₄ used as internal standard and incubation in phosphate buffer pH = 9.5, 20 mg of hair samples were extracted with liquid/liquid extraction. Linearity was verified for all compounds between 0.5 and 50 and 2000 pg/mg. LOD and LOQ were determined between 0.1-20 and 0.5-50 pg/mg respectively, according to the various analytes. Intra- and inter-day precision (CV < 20%), matrix effects and recovery were evaluated for all compounds with CVs < 20%. The application and the interest of SARMs screening was demonstrated in a doping case. Three SARMs were detected namely andarine (120-1644 pg/mg), ostarine (1-9 pg/mg) and S23 (0.6-16 pg/mg) in 6x1 cm segments of the subject.

2021-02-01·Journal of Pharmaceutical and Biomedical Analysis3区 · 医学

Simultaneous detection of different chemical classes of selective androgen receptor modulators in urine by liquid chromatography-mass spectrometry-based techniques

3区 · 医学

Article

作者: Mazzarino, Monica ; Stacchini, Carlotta ; Ricci, Matteo ; Dima, Anna Pia ; de la Torre, Xavier ; Botrè, Francesco ; Comunità, Fabio

Analytical procedures to detect the misuse of selective androgen receptor modulators in human urine, targeting either the parent drugs and/or their main metabolites, were developed and validated. In detail, 19 target compounds belonging to 9 different chemical classes were considered: arylpropionamide (i.e., andarine (S4), ostarine (S22), S1, S6, S9 and S23), diarylhydantoin (i.e., GLPG0492), indole (i.e., LY2452473, GSK2881078), isoquinoline-carbonyle (i.e., PF-02620414), phenyl-oxadiazole (i.e., RAD140), pyrrolidinyl-benzonitrile (i.e., LGD4033), quinolinone (i.e., LGD2226, LGD3303), steroidal (i.e., Cl-4AS-1, MK0773 and TFM-4AS-1), and tropanol (i.e., AC-262536 and ACP105) derivatives. The metabolites of the target compounds considered were enzymatically synthesized by using human liver microsomes. Sample pre-treatment included enzymatic hydrolysis followed by liquid-liquid extraction at neutral pH. The instrumental analysis was performed by ultra-high-performance liquid chromatography coupled to either high- or low-resolution mass spectrometry. Validation was performed according to the ISO 17025 and the World Anti-Doping Agency guidelines. The analyses carried out on negative samples confirmed the method's selectivity, not showing any significant interferences at the retention times of the analytes of interest. Detection capability was determined in the range of 0.1-1.0 ng/mL for the screening procedure and 0.2-1.0 ng/mL for the confirmation procedure (except for GLPG0492 and GSK2881078). The recovery was greater than 80 % for all analytes, and the matrix effect was smaller than 35 %. The method also matched the criteria of the World Anti-Doping Agency in terms of repeatability of the relative retention times (CV% < 1.0) and of the relative abundances of the selected ion transitions (performed only in the case of triple quadrupole, CV% < 15), ensuring the correct identification of all the analytes considered. Urine samples containing andarine, ostarine, or LGD4033 were used to confirm the actual applicability of the selected analytical strategies. All target compounds (parent drugs and their main metabolites) were detected and correctly identified.

2018-03-01·Molecular and Cellular Endocrinology2区 · 医学

Detection of SARMs in doping control analysis

2区 · 医学

Review

作者: Thevis, Mario ; Schänzer, Wilhelm

The class of selective androgen receptor modulators (SARMs) has been the subject of intense and dedicated clinical research over the past two decades. Potential therapeutic applications of SARMs are manifold and focus particularly on the treatment of conditions manifesting in muscle loss such as general sarcopenia, cancer-associated cachexia, muscular dystrophy, etc. Consequently, based on the substantial muscle- and bone-anabolic properties of SARMs, these agents constitute substances with significant potential for misuse in sport and have therefore been added to the Word Anti-Doping Agency's (WADA's) Prohibited List in 2008. Since then, numerous adverse analytical findings have been reported for various different SARMs, which has underlined the importance of proactive and preventive anti-doping measures concerning emerging drugs such as these anabolic agents, which have evidently been misused in sport despite the fact that none of these SARMs has yet received full clinical approval. In this review, analytical data on SARMs generated in the context of research conducted for sports drug testing purposes are summarized and state-of-the-art test methods aiming at intact drugs as well as diagnostic urinary metabolites are discussed. Doping control analytical approaches predominantly rely on chromatography hyphenated to mass spectrometry, which have allowed for appropriately covering the considerable variety of pharmacophores present in SARMs such as the non-steroidal representatives ACP-105, BMS-564929, GLPG0492 (DT-200), LG-121071, LGD-2226, LGD-4033/VK 5211, ostarine/enobosarm, RAD-140, S-40503, etc. as well as steroidal compounds such as MK-0773 and YK-11.

100 项与 MK-0773 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	MK-0773	-	DB16244

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
肌肉减少症	临床2期	美国	Merck & Co., Inc.	2007-09-30
肌肉减少症	临床2期	美国	Merck & Co., Inc.	2007-09-30
肌肉萎缩	临床2期	英国	Merck GmbH	-
肌肉萎缩	临床2期	瑞典	Merck GmbH	-
肌肉萎缩	临床2期	美国	Merck GmbH	-
肌肉萎缩	临床2期	法国	Merck GmbH	-
肌肉萎缩	临床2期	西班牙	Merck GmbH	-
肌肉萎缩	临床2期	丹麦	Merck GmbH	-
肌肉萎缩	临床2期	意大利	Merck GmbH	-
肌肉萎缩	药物发现	芬兰	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


NCT00529659 (CTgov)	临床2期	肌肉减少症	170	Comparator: MK-0773 (MK-0773)	(積觸衊窪鹹醖襯膚蓋淵) = 夢觸齋構範簾願艱積壓鏇鹽淵鹽蓋餘艱築製衊 (膚鬱製築淵襯願憲憲壓, 鏇鏇鏇夢獵餘壓鏇艱醖 ~ 願鏇齋繭廠觸繭鏇願夢) 更多	-	2012-07-02
				Comparator: Placebo (Placebo)	(積觸衊窪鹹醖襯膚蓋淵) = 鬱鬱獵願鬱願衊鏇艱衊鏇鹽淵鹽蓋餘艱築製衊 (膚鬱製築淵襯願憲憲壓, 餘憲築壓製蓋築衊蓋鑰 ~ 襯蓋壓齋鹹衊醖醖壓顧) 更多