MK-1903

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H8N2O2
Molecular Weight	164.1613
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)C1=NNC2=C1C[C@H]3C[C@@H]23

InChI

InChIKey=CUTZNERBKDMLAP-QWWZWVQMSA-N

InChI=1S/C8H8N2O2/c11-8(12)7-5-2-3-1-4(3)6(5)9-10-7/h3-4H,1-2H2,(H,9,10)(H,11,12)/t3-,4-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22914621
Curator's Comment: description was created based on several sources, including http://www.prnewswire.com/news-releases/arena-pharmaceuticals-announces- merck-discontinues-development-of-investigational-niacin-receptor-agonist-program-for-atherosclerosis-80009722.html

MK-1903 is a potent and selective hydroxycarboxylic acid receptor 2 (HCA2, GPR109A) full agonist. Exhibits no binding at the GRP109B receptor. This drug had been in phase II clinical trial for the treatment of atherosclerosis and Dyslipidemia. But then, according to Merck, elevation of HDL cholesterol relative to placebo did not meet the trial's pre-specified primary objective for efficacy; no safety signals were implicated as drivers of the decision to discontinue development.

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/22435740	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dyslipidemia 34 Sources: https://clinicaltrials.gov/ct2/show/NCT00847197	Primary		Phase II 1147	Unknown Approved Use Unknown
Atherosclerosis 76 Sources: https://www.merck.com/research/pipeline/MerckPipeline_Oct09_Final_10-15-09_10-Q.pdf	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
49.8 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22435740	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-1903 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
56.3 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22435740	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1903 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
44.9 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22435740	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-1903 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
119.2 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22435740	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-1903 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
113.7 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22435740	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1903 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
87.9 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22435740	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-1903 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22435740	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MK-1903 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22435740	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MK-1903 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
A2B Chem	AX59635	http://a2bchem.com/prod/AX59635
ApexBio Technology	B5658	https://www.apexbt.com/catalogsearch/result/?q=B5658
Chemspace	CSC009924904	https://chem-space.com/CSC009924904
Chemspace	CSC015596462	https://chem-space.com/CSC015596462
Chemspace	CSC015638276	https://chem-space.com/CSC015638276
Chemspace	CSC016150759	https://chem-space.com/CSC016150759
eMolecules	96783119	https://orderbb.emolecules.com/search/#?query=96783119
eMolecules	96965968	https://orderbb.emolecules.com/search/#?query=96965968
Enamine	BBV-39941828	http://www.enaminestore.com/catalog/BBV-39941828
Enamine	BBV-45439126	http://www.enaminestore.com/catalog/BBV-45439126
Enamine	BBV-77594193	http://www.enaminestore.com/catalog/BBV-77594193
Enamine	BBV-77614578	http://www.enaminestore.com/catalog/BBV-77614578
Enamine	EN300-2008229	https://www.enaminestore.com/catalog/EN300-2008229
MolPort	MolPort-035-765-775	https://www.molport.com/shop/molecule-link/MolPort-035-765-775
MuseChem	I008050	https://www.musechem.com/product/I008050.html
Norris Pharm	NSZB-A242680
Tocris	4622	https://www.tocris.com/search.php?Type=QuickSearch&Value=4622

PubMed

Title	Date	PubMed
Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity.	2014-12	25463108
Niacin lipid efficacy is independent of both the niacin receptor GPR109A and free fatty acid suppression.	2012-08-22	22914621
(1aR,5aR)1a,3,5,5a-Tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (MK-1903): a potent GPR109a agonist that lowers free fatty acids in humans.	2012-04-26	22435740

Patents

Sample Use Guides

In Vivo Use Guide

Three 50 mg capsules MK1903 by mouth every 8 hours for 4 weeks. All participants will receive placebo for a 2 week run-in period.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

(4AR,5AR)-4,4A,5,5A-TETRAHYDRO-1H-CYCLOPROPA(4,5)CYCLOPENTA(1,2-C)PYRAZOLE-3-CARBOXYLIC ACID

Preferred Name

English

MK-1903

Common Name

English

1H-CYCLOPROPA(4,5)CYCLOPENTA(1,2-C)PYRAZOLE-3-CARBOXYLIC ACID, 4,4A,5,5A-TETRAHYDRO-, (4AR,5AR)-

Systematic Name

English

Code System Code Type Description

CAS

1268882-43-4

Created by admin on Tue Apr 01 16:56:21 GMT 2025 , Edited by admin on Tue Apr 01 16:56:21 GMT 2025

PRIMARY

PUBCHEM

49763030

Created by admin on Tue Apr 01 16:56:21 GMT 2025 , Edited by admin on Tue Apr 01 16:56:21 GMT 2025

PRIMARY

MANUFACTURER PRODUCT INFORMATION

MK-1903

Created by admin on Tue Apr 01 16:56:21 GMT 2025 , Edited by admin on Tue Apr 01 16:56:21 GMT 2025

PRIMARY

Biological Activity: Potent and selective hydroxycarboxylic acid receptor 2 (HCA2, GPR109A) full agonist; exhibits greater potency than niacin in a whole cell HTRF-cAMP assay (EC50 values are 12.9 and 51 nM respectively). Exhibits no binding at the GRP109B receptor.

FDA UNII

62N05GRI0P

Created by admin on Tue Apr 01 16:56:21 GMT 2025 , Edited by admin on Tue Apr 01 16:56:21 GMT 2025

PRIMARY

ACTIVE MOIETY


					62N05GRI0P

MK-1903

Details

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Cmax

AUC

T1/2

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2