MK1064 | MK-1064 | CAS#1207253-08-4 | Orexin OX2 Receptor Antagonist

MK-1064
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 530433

CAS#: 1207253-08-4

Description: MK-1064 is a potent, selective and orally active Orexin OX2 Receptor Antagonist for potential treatment of insomnia. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy.

Chemical Structure

MK-1064

CAS# 1207253-08-4

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 530433
Name: MK-1064
CAS#: 1207253-08-4
Chemical Formula: C24H20ClN5O3
Exact Mass: 461.13
Molecular Weight: 461.906
Elemental Analysis: C, 62.41; H, 4.36; Cl, 7.67; N, 15.16; O, 10.39

Price and Availability

Size	Price	Availability
10mg	USD 160	Ready to ship
25mg	USD 350	Ready to ship
50mg	USD 550	Ready to ship
100mg	USD 950	Ready to ship
200mg	USD 1650	Ready to ship
500mg	USD 2450	Ready to ship
1g	USD 3450	Ready to ship
2g	USD 5950	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: MK1064; MK-1064; MK 1064.

IUPAC/Chemical Name: 5-(5-Chloro-3-pyridyl)-N-((5,6-dimethoxy-2-pyridyl)methyl)-2-(2-pyridyl)pyridine-3-carboxamide

InChi Key: CKTWQGHVNRYNCM-UHFFFAOYSA-N

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)

SMILES Code: O=C(C1=CC(C2=CC(Cl)=CN=C2)=CN=C1C3=NC=CC=C3)NCC4=NC(OC)=C(OC)C=C4

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#A9T08K10
View CoA: current batch, Lot#A21T08K15

QC Data:

View QC data: current batch, Lot#A9T08K10
View QC data: current batch, Lot#A21T08K15

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	MK-1064 is a selective orexin 2 receptor antagonist which targets 2-SORA.
In vitro activity:	TBD
In vivo activity:	The contribution of orexin receptor signaling in both struggle behavior and body weight change in response to restraint stress was determined through use of a selective OX2R antagonist, MK-1064. Specifically, after DREADDs’ expression, rats underwent five consecutive days of 30-min restraint, with either vehicle or CNO to stimulate DREADDs prior to each restraint, and with either vehicle or MK-1064 to antagonize the orexin 2 receptor (paradigm depicted in Fig. 3A). Struggle behavior indicates the number of attempts to escape during restraint, which is an important component of the stress response and habituates with repeated restraint (Grissom et al., 2008). As demonstrated in Fig. 3B, the CNO/vehicle group spent significantly more time struggling than the other three treatment groups. Essentially, stimulating orexins with CNO increases struggle behavior, and blocking OX2R with MK-1064 reverses this effect. Coincident with changes observed in struggle behavior, body weight decreased from the first to the last day of restraint in levels of high orexin, but this was eliminated with MK-1064 pretreatment (Fig. 3C). Thus, while all rats lost weight over the 5 days of restraint stress, further stimulating orexins prior to each 30-min restraint exacerbated this effect and these results appear mediated through OX2R. Pretreatment with MK-1064, however, significantly attenuated the ACTH response in combination with either vehicle (Fig. 4B), or CNO pre-treatment (Fig. 4C), indicating that OX2R is responsible for mediating at least part of the ACTH response to acute restraint. Importantly, the ACTH response was similarly attenuated by MK-1064 in either the presence or absence of CNO (Fig. 4D), indicating that activation of orexin signaling through mechanisms not involving OX2R contributes little to the ACTH response on this first day of restraint stress. The results from this study improve the understanding of the role of orexin receptors in regulating the HPA response to both acute and repeated stress. The involvement of OX2R in acute stress has been confirmed. Reference: Neuroscience. 2017 Apr 21; 348: 313–323. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322837/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	60.0	129.90

Preparing Stock Solutions

The following data is based on the product molecular weight 461.91 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Amodeo LR, Wills DN, Sanchez-Alavez M, Ehlers CL. Effects of an Orexin-2 Receptor Antagonist on Sleep and Event-Related Oscillations in Female Rats Exposed to Chronic Intermittent Ethanol During Adolescence. Alcohol Clin Exp Res. 2020 Jul;44(7):1378-1388. doi: 10.1111/acer.14361. Epub 2020 Jun 12. PMID: 32424852; PMCID: PMC7720846. 2. Grafe LA, Eacret D, Luz S, Gotter AL, Renger JJ, Winrow CJ, Bhatnagar S. Orexin 2 receptor regulation of the hypothalamicpituitary-adrenal (HPA) response to acute and repeated stress. Neuroscience. 2017 Apr 21;348:313-323. doi: 10.1016/j.neuroscience.2017.02.038. Epub 2017 Feb 28. PMID: 28257896; PMCID: PMC6322837.
In vitro protocol:	TBD
In vivo protocol:	1. Amodeo LR, Wills DN, Sanchez-Alavez M, Ehlers CL. Effects of an Orexin-2 Receptor Antagonist on Sleep and Event-Related Oscillations in Female Rats Exposed to Chronic Intermittent Ethanol During Adolescence. Alcohol Clin Exp Res. 2020 Jul;44(7):1378-1388. doi: 10.1111/acer.14361. Epub 2020 Jun 12. PMID: 32424852; PMCID: PMC7720846. 2. Grafe LA, Eacret D, Luz S, Gotter AL, Renger JJ, Winrow CJ, Bhatnagar S. Orexin 2 receptor regulation of the hypothalamicpituitary-adrenal (HPA) response to acute and repeated stress. Neuroscience. 2017 Apr 21;348:313-323. doi: 10.1016/j.neuroscience.2017.02.038. Epub 2017 Feb 28. PMID: 28257896; PMCID: PMC6322837.

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1: Jacobson LH, Chen S, Mir S, Hoyer D. Orexin OX(2) Receptor Antagonists as Sleep Aids. Curr Top Behav Neurosci. 2016 Dec 2. [Epub ahead of print] PubMed PMID: 27909987.

2: Gao M, Wang M, Zheng QH. Synthesis of [(11)C]MK-1064 as a new PET radioligand for imaging of orexin-2 receptor. Bioorg Med Chem Lett. 2016 Aug 1;26(15):3694-9. doi: 10.1016/j.bmcl.2016.05.083. PubMed PMID: 27268698.

3: Gotter AL, Forman MS, Harrell CM, Stevens J, Svetnik V, Yee KL, Li X, Roecker AJ, Fox SV, Tannenbaum PL, Garson SL, Lepeleire ID, Calder N, Rosen L, Struyk A, Coleman PJ, Herring WJ, Renger JJ, Winrow CJ. 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. PubMed PMID: 27256922; PubMed Central PMCID: PMC4891657.

4: Roecker AJ, Mercer SP, Schreier JD, Cox CD, Fraley ME, Steen JT, Lemaire W, Bruno JG, Harrell CM, Garson SL, Gotter AL, Fox SV, Stevens J, Tannenbaum PL, Prueksaritanont T, Cabalu TD, Cui D, Stellabott J, Hartman GD, Young SD, Winrow CJ, Renger JJ, Coleman PJ. Discovery of 5''-chloro-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2,2':5',3''-terpyridine-3'-carbo xamide (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. PubMed PMID: 24376006.

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