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
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
| Molecular Formula | C8H8N2O2 |
| Molecular Weight | 164.1613 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator'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
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
Cmax
| Value | Dose | Co-administered | 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 | Co-administered | 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 |
T1/2
| 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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity. | 2014-12 |
|
| Niacin lipid efficacy is independent of both the niacin receptor GPR109A and free fatty acid suppression. | 2012-08-22 |
|
| (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 |
Sample Use Guides
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
| Substance Class |
Chemical
Created
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admin
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Tue Apr 01 16:56:21 GMT 2025
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Tue Apr 01 16:56:21 GMT 2025
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| Record UNII |
62N05GRI0P
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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
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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. | ||
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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
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
Compound R,R-19a (MK-1903) was advanced through preclinical studies, was well tolerated, and presented no apparent safety concerns. Compound R,R-19a was advanced into a phase 1 clinical trial and produced a robust decrease in plasma free fatty acids. On the basis of these results, R,R-19a was evaluated in a phase 2 study in humans. Because R,R-19a produced only a weak effect on serum lipids as compared with niacin, we conclude that the beneficial effects of niacin are most likely the result of an undefined GPR109a independent pathway.
In table 3. is found the pharmacokinetics of compounds R,R-19a and R,S-endo-19b in several species.
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ACTIVE MOIETY |
Originator: Arena Pharmaceuticals; Developer: Merck & Co; Class: Cardiovascular therapy; Mechanism of Action: G protein-coupled receptor agonist, Nicotinic receptor agonist; Highest Development Phases: Discontinued for Atherosclerosis, Lipid metabolism disorders; Most Recent Events: 24 Dec 2009 Discontinued - Phase-II for Lipid metabolism disorders in USA (PO), 24 Dec 2009 Discontinued - Phase-I for Atherosclerosis in USA (PO), 18 Feb 2009 Merck & Co initiates enrolment in a phase II trial for Lipid disorders in USA
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