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mk-1064

Product Namemk-1064
CAS1207253-08-4
MFC24H20ClN5O3
MW461.9
EINECS
MOL File1207253-08-4.mol

Chemical Properties

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

Safety Information

HS Code

2933399990

Usage And Synthesis

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 (30mg/kg, oral administration) promotes sleep in rodents selectively through OX2R in Wild-type mice^[2].
MK-1064 (30mg/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 3.5hours 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)	t_1/2 (h)	Dose (mg/kg)	C_max (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

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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