MK-0354

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H8N6
Molecular Weight	176.1786
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CC2=C(C1)C(=NN2)C3=NN=NN3

InChI

InChIKey=LTQYSJKGRPGMPO-UHFFFAOYSA-N

InChI=1S/C7H8N6/c1-2-4-5(3-1)8-9-6(4)7-10-12-13-11-7/h1-3H2,(H,8,9)(H,10,11,12,13)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18665582
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21291763

MK-0354 is a GPR109a (Niacin receptor 1) agonist, originated by Arena Pharmaceuticals. In phase II of clinical trials against dyslipidemia treatment with MK-0354 failed to produce changes in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or triglycerides.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hydroxycarboxylic acid receptor 2 28 Target ID: CHEMBL3785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18665582	Agonist 2752		505.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dyslipidemia 34 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21291763	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
208 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763/	2400 mg single, oral dose: 2400 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
373 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: food status: FASTED
351 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	3600 mg single, oral dose: 3600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
147 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	1800 mg 2 times / day multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
235 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	1800 mg 2 times / day multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
458 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763/	2400 mg single, oral dose: 2400 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
766 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: food status: FASTED
731 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	3600 mg single, oral dose: 3600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
392 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	1800 mg 2 times / day multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
457 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	1800 mg 2 times / day multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763/	2400 mg single, oral dose: 2400 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	3600 mg 1 times / day multiple, oral dose: 3600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: food status: FASTED
7.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	3600 mg single, oral dose: 3600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	1800 mg 2 times / day multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
9.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21291763	1800 mg 2 times / day multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0354 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00G47Y	https://www.1pchem.com/search?query=1P00G47Y
AChemBlock	10084	http://www.achemblock.com/catalogsearch/result/?q=10084
AstaTech	91749	http://astatechinc.com/CPSResult.php?CRNO=91749
Axon MedChem	1576	https://www.axonmedchem.com/product/1576
BLD Pharm	BD630903	http://www.bldpharm.com/search/Search.html?keyword=BD630903
Chem Scene	CS-4589	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4589
Debye Scientific	DA-02747	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-02747
eMolecules	106930138	https://orderbb.emolecules.com/search/#?query=106930138
eMolecules	33560960	https://orderbb.emolecules.com/search/#?query=33560960
Enamine	BBV-39698120	http://www.enaminestore.com/catalog/BBV-39698120
Enamine	BBV-93494330	http://www.enaminestore.com/catalog/BBV-93494330
Hairui	HR104180	http://www.hairuichem.com/en/product/search.do?q=HR104180
Lab Network	LN01342049	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342049
mcule	MCULE-3020799484	https://mcule.com/MCULE-3020799484/
MedChem Express	HY-13008	https://www.medchemexpress.com/search.html?q=HY-13008&ft=&fa=&fp=
Molnova	M16190	https://www.molnova.com/en/serch-list.html?keywords=M16190
MolPort	MolPort-009-683-033	https://www.molport.com/shop/molecule-link/MolPort-009-683-033
ShangHai Biochempartner	BCP18112	http://www.biochempartner.com/search_BCP18112

PubMed

Title	Date	PubMed
beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice.	2009-05	19349687
3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): a partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice.	2008-08-28	18665582

Patents

Sample Use Guides

In Vivo Use Guide

In a phase II study MK-0354 was administred daily at dose 2.5g for 4 weeks.

Route of Administration: Oral

In Vitro Use Guide

Equilibrium binding of [3H]nicotinic acid was done with membranes (30 μg/assay) from CHO-K1 cells, transfected with GPR109a, and test compound diluted in assay buffer (20 mM HEPES, pH 7.4, 1 mM MgCl2, and 0.01% CHAPS) in a total volume of 200 uL. After 4 h at room temperature, reactions were filtered through Packard Unifilter GF/C plates using a Packard Harvester and washed eight times with 200 μl of ice-cold binding buffer. Nonspecific binding was determined in the presence of 250 μM unlabeled nicotinic acid. Competitive binding assays were performed in the presence of 50 nM [3H]nicotinic acid.

Name

Type

Language

3-(1H-TETRAZOL-5-YL)-1,4,5,6-TETRAHYDROCYCLOPENTA(C)PYRAZOLE

Preferred Name

English

MK-0354

Code

English

CYCLOPENTA(C)PYRAZOLE, 1,4,5,6-TETRAHYDRO-3-(1H-TETRAZOL-5-YL)-

Systematic Name

English

Code System Code Type Description

CAS

851776-28-8