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1mg |
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5mg |
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10mg |
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25mg |
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250mg |
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MK-1064 (MK1064) is a novel, potent, selective and orally bioavailable antagonist of Orexin OX2 Receptor (OX2R), with the potential to be used for the treatment of insomnia. Orexin receptors (OX1R, OX2R) are the primary mediators of arousal promotion, and they are used by orexin neuropeptides to control sleep/wake cycles. An antagonist of OX2R singlet is MK-1064. MK-1064 has been shown in preclinical settings to enhance sleep in rats by increasing both REM and NREM sleep at OX2R occupancies higher than those seen with dual orexin receptor antagonists. Like dual antagonists, MK-1064 helps dogs sleep longer in both NREM and REM phases without making them cataplexy. MK-1064 demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep.
Targets |
OX1 ( IC50 = 1789 nM ); OX2 ( IC50 = 18 nM ); OX1 ( Ki = 1584 nM ); OX2 ( Ki = 0.5 nM )
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ln Vitro |
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ln Vivo |
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Animal Protocol |
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References |
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Molecular Formula |
C24H20CLN5O3
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Molecular Weight |
461.91
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Exact Mass |
461.13
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Elemental Analysis |
C, 62.41; H, 4.36; Cl, 7.67; N, 15.16; O, 10.39
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CAS # |
1207253-08-4
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Related CAS # |
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Appearance |
Solid powder
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SMILES |
COC1=C(N=C(C=C1)CNC(=O)C2=C(N=CC(=C2)C3=CC(=CN=C3)Cl)C4=CC=CC=N4)OC
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InChi Key |
CKTWQGHVNRYNCM-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C24H20ClN5O3/c1-32-21-7-6-18(30-24(21)33-2)14-29-23(31)19-10-16(15-9-17(25)13-26-11-15)12-28-22(19)20-5-3-4-8-27-20/h3-13H,14H2,1-2H3,(H,29,31)
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Chemical Name |
5-(5-chloropyridin-3-yl)-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2-pyridin-2-ylpyridine-3-carboxamide
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.1649 mL | 10.8246 mL | 21.6492 mL | |
5 mM | 0.4330 mL | 2.1649 mL | 4.3298 mL | |
10 mM | 0.2165 mL | 1.0825 mL | 2.1649 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02549014 | Completed | Drug: MK-1064 Drug: Placebo |
Pharmacokinetics | Merck Sharp & Dohme LLC | July 6, 2009 | Phase 1 |
NCT02549027 | Completed | Drug: MK-1064 Drug: Placebo Drug: MK-6096 |
Polysomnography | Merck Sharp & Dohme LLC | November 6, 2009 | Phase 1 |
MK-1064 dose-dependently promotes somnolence and attenuates arousal in healthy human subjects.Sci Rep.2016 Jun 3;6:27147. th> |
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MK-1064 promotes sleep in healthy subjects.Sci Rep.2016 Jun 3;6:27147. td> |
Sleep effects of MK-1064 30 mg/kg are OX2R-dependent. Enrolment information for Phase I studies in healthy human volunteers.Sci Rep.2016 Jun 3;6:27147. td> |
MK-1064 dose-dependently promotes both NREM and REM sleep during the active phase in rats.Sci Rep.2016 Jun 3;6:27147. th> |
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MK-1064 requires higher OX2R occupancies to promote sleep relative to DORA-12 in rats.Sci Rep.2016 Jun 3;6:27147. td> |
MK-1064 effectively promotes somnolence but not cataplexy in canines.Sci Rep.2016 Jun 3;6:27147. td> |