[CAS NO. 1207253-08-4] MK-1064
PRODUCTS SPECIFICATIONS [1207253-08-4]
DESCRIPTION [1207253-08-4]
Overview
| MDL | MFCD28502027 |
|---|---|
| Molecular Weight | 461.90 |
| Molecular Formula | C24H20ClN5O3 |
| SMILES | O=C(C1=CC(C2=CC(Cl)=CN=C2)=CN=C1C3=NC=CC=C3)NCC4=NC(OC)=C(OC)C=C4 |
2 Publications Citing Use of MCE
Summary
IC50 & Target
|
OX 2 Receptor 18 nM (IC 50 ) |
OX 1 Receptor 1789 nM (IC 50 ) |
OX 2 Receptor 0.5 nM (Ki) |
OX 1 Receptor 1584 nM (Ki) |
In Vivo
MK-1064 (30 mg/kg, oral administration) promotes sleep in rodents selectively through OX2R in Wild-type mice
[2]
.
MK-1064 (30 mg/kg, oral administration, 5 days) reverses the struggle behavior induced by CNO pre-treatment in rats
[3]
.
MK-1064 (1-5 mg/kg, intravenous injection/oral administration) shows moderate oral bioavailability and clearance in rat, dog, and rhesus monkey
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Wild-type and OX 2 R knockout mice [2] |
| Dosage: | 30 mg/kg |
| Administration: | Oral administration |
| Result: | Displayed active wake reduction accompanied by significant increases in SWS (slow-wave sleep) and REM (rapid eye movement) at time points up to 3.5 hours following treatment. |
| Animal Model: | Rat, dog, and rhesus monkey (Pharmacokinetics assay) [1] | ||||||||||||||||||||||||||||
| Dosage: | 1, 2, 3, 5 mg/kg | ||||||||||||||||||||||||||||
| Administration: | Oral administration (P.O.), intravenous injection (I.V.) | ||||||||||||||||||||||||||||
| Result: |
Pharmacokinetics profile of MK-1064.
|
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02549027 | Merck Sharp & Dohme LLC |
Polysomnography
|
November 6, 2009 | Phase 1 |
| NCT02549014 | Merck Sharp & Dohme LLC |
Pharmacokinetics
|
July 6, 2009 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 50 mg/mL ( 108.25 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1650 mL | 10.8249 mL | 21.6497 mL |
| 5 mM | 0.4330 mL | 2.1650 mL | 4.3299 mL |
| 10 mM | 0.2165 mL | 1.0825 mL | 2.1650 mL |
-
1.
References
- [1] Roecker AJ et al. Discovery of 5''-chloro-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2,2':5',3''-terpyridine-3'-carboxamide (MK-1064): a selective orexin 2 receptor antagonist (2-SORA) for the treatment of insomnia. ChemMedChem. 2014 Feb;9(2):311-22.
- [2] Gotter AL et al. Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man. Sci Rep. 2016 Jun 3;6:27147.
- [3] Laura A Grafe, et al. Orexin 2 receptor regulation of the hypothalamic-pituitary-adrenal (HPA) response to acute and repeated stress. Neuroscience. 2017 Apr 21;348:313-323.
