| Identification | Back Directory | [Name]
mk-1064 | [CAS]
1207253-08-4 | [Synonyms]
mk-1064
CS-2221
MK1064;MK 1064
MK-1064, CID 44633765
MK-1064(Urokinase inhibitor 1)
5''-Chloro-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2,2':5',3''-terpyridine-3'-carboxamide
[2,2':5',3''-Terpyridine]-3'-carboxamide, 5''-chloro-N-[(5,6-dimethoxy-2-pyridinyl)methyl]-
5-(5-CHLOROPYRIDIN-3-YL)-N-[(5,6-DIMETHOXYPYRIDIN-2-YL)METHYL]-2-PYRIDIN-2-YLPYRIDINE-3-CARBOXAMIDE | [Molecular Formula]
C24H20ClN5O3 | [MOL File]
1207253-08-4.mol | [Molecular Weight]
461.9 |
| Chemical Properties | Back Directory | [Boiling point ]
662.4±55.0 °C(Predicted) | [density ]
1.305±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:60.0(Max Conc. mg/mL);129.9(Max Conc. mM) | [form ]
A crystalline solid | [pka]
11.98±0.46(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
MK-1064 is a selective and orally active OX2R antagonist (Ki: 0.5 nM, IC50: 18 nM). MK-1064 promotes sleep in vivo. MK-1064 can be used in the research of insomnia[1][3]. | [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].
| Animal Model: | Wild-type and OX2R 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.
| Species | Dose (mg/kg) | CL (mL/min/kg) | t1/2 (h) | Dose (mg/kg) | Cmax (μM) | F (%) | | Rat | 2 (I.V.) | 39 | 0.3 | 5 (P.O.) | 1.5 | 54 | |
| Dog | 1 (I.V.) | 16 | 1.0 | 3 (P.O.) | 1.0 | 48 | |
| Rhesus | 2 (I.V.) | 12 | 0.8 | 5 (P.O.) | 0.9 | 16 |
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| [IC 50]
OX2 Receptor: 18 nM (IC50); OX1 Receptor: 1789 nM (IC50); OX2 Receptor: 0.5 nM (Ki); OX1 Receptor: 1584 nM (Ki) | [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. DOI:10.1002/cmdc.201300447
[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. DOI:10.1038/srep27147
[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. DOI:10.1016/j.neuroscience.2017.02.038 |
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