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
[H][C@]12C[C@@]1([H])C3=C(C2)C(=NN3)C(O)=O
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
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 |
|---|---|---|---|---|
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 |
|
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| (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 Apr 26 |
|
| Niacin lipid efficacy is independent of both the niacin receptor GPR109A and free fatty acid suppression. | 2012 Aug 22 |
|
| Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity. | 2014 Dec |
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
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1268882-43-4
Created by
admin on Sat Dec 16 11:46:03 UTC 2023 , Edited by admin on Sat Dec 16 11:46:03 UTC 2023
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49763030
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admin on Sat Dec 16 11:46:03 UTC 2023 , Edited by admin on Sat Dec 16 11:46:03 UTC 2023
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MK-1903
Created by
admin on Sat Dec 16 11:46:03 UTC 2023 , Edited by admin on Sat Dec 16 11:46:03 UTC 2023
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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 Sat Dec 16 11:46:03 UTC 2023 , Edited by admin on Sat Dec 16 11:46:03 UTC 2023
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ACTIVE MOIETY
