Delving into the Latest Updates on MK-0773 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

AR

Mechanism

AR modulators(Androgen Receptor modulators)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Muscular AtrophyOsteoporosisSarcopenia

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck GmbH

Merck Sharp & Dohme Corp.

GTx, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC27H34FN5O2

InChIKeyGBEUKTWTUSPHEE-JWJWXJQQSA-N

CAS Registry606101-58-0

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.

01 Feb 2021·Journal of Pharmaceutical and Biomedical AnalysisQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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.

01 Mar 2018·Molecular and Cellular EndocrinologyQ2 · MEDICINE

Detection of SARMs in doping control analysis

Q2 · MEDICINE

Review

Author: 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 Deals associated with MK-0773

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External Link

KEGG	Wiki	ATC	Drug Bank
-	MK-0773	-	DB16244

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Sarcopenia	Phase 2	-	Merck Sharp & Dohme Corp.	01 Oct 2007
Osteoporosis	Phase 2	-	Merck Sharp & Dohme Corp.	01 Nov 2005
Muscular Atrophy	Phase 2	ES	Merck GmbH	-
Muscular Atrophy	Phase 2	SE	Merck GmbH	-
Muscular Atrophy	Phase 2	FI	Merck GmbH	-
Muscular Atrophy	Phase 2	IT	Merck GmbH	-
Muscular Atrophy	Phase 2	DK	Merck GmbH	-
Muscular Atrophy	Phase 2	FR	Merck GmbH	-
Muscular Atrophy	Phase 2	GB	Merck GmbH	-
Muscular Atrophy	Phase 2	US	Merck GmbH	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00529659 (0773-005, CTgov)	Phase 2	Sarcopenia	170	Comparator: MK-0773 (MK-0773)	xpbzzhigcu(ztvkdxetwj) = eypdfsqhkf lxjthlqoit (namdiqahis, xgoxftnaej - jmyhzjwksy) View more	-	02 Jul 2012
				Comparator: Placebo (Placebo)	xpbzzhigcu(ztvkdxetwj) = droobprwgi lxjthlqoit (namdiqahis, fieovvadgk - wiaarivulx) View more