MK-1064

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H20ClN5O3
Molecular Weight	461.9
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(CNC(=O)C2=CC(=CN=C2C3=NC=CC=C3)C4=CN=CC(Cl)=C4)N=C1OC

InChI

InChIKey=CKTWQGHVNRYNCM-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27909987 | https://www.ncbi.nlm.nih.gov/pubmed/24376006 | https://www.ncbi.nlm.nih.gov/pubmed/27268698

MK-1064 is an orexin 2 receptor antagonist patented by pharmaceutical company Merck & Co for the treatment of insomnia. MK-1064decreases the amount of time spent in active wake and increases the time spent in rapid eye movement (REM) sleep and slow-wave sleep (SMS) in mice, rats, dogs, and rhesus monkeys. MK-1064, even at the very high dose did not show signs of an enhanced predisposition to cataplexy in the food-elicited cataplexy test. MK-1064 has now completed two Phase I studies focused on pharmacokinetics, safety and sleep in healthy volunteers. The effects of MK-1064 on sleep parameters were moderate, but statistically significant, representing the first demonstration of PSG-quantified sleep induced in humans by an OX2R antagonist. MK-1064 at 50, 120 and 250 mg decreased latency to persistent sleep and wake after sleep onset, and increased total sleep time and sleep efficiency.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Orexin receptor 1 8 Target ID: CHEMBL5113 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26317591	Antagonist 2849		1789.0 nM [IC50]
Orexin receptor 2 10 Target ID: CHEMBL4792 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26317591	Antagonist 2849		18.0 nM [IC50]

C_max

Value	Dose	Analyte	Population
0.37 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.42 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.06 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.09 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.6 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.83 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.78 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.28 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1.95 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.67 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.22 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.45 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
20.93 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
23.5 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
48.93 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
51.48 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
11.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-1064 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

PubMed

Title	Date	PubMed
Synthesis of [(11)C]MK-1064 as a new PET radioligand for imaging of orexin-2 receptor.	2016-08-01	27268698

Patents

Sample Use Guides

In Vivo Use Guide

50, 120 and 250 mg

Route of Administration: Oral

Name

Type

Language

MK-1064

Common Name

English

MK 1064

Preferred Name

English

5''-CHLORO-N-((5,6-DIMETHOXYPYRIDIN-2-YL)METHYL)-2,2':5',3''-TERPYRIDINE-3'-CARBOXAMIDE

Systematic Name

English

(2,2':5',3''-TERPYRIDINE)-3'-CARBOXAMIDE, 5''-CHLORO-N-((5,6-DIMETHOXY-2-PYRIDINYL)METHYL)-

Systematic Name

English

5-(5-CHLORO-3-PYRIDYL)-N-((5,6-DIMETHOXY-2-PYRIDYL)METHYL)-2-(2-PYRIDYL)PYRIDINE-3-CARBOXAMIDE

Systematic Name

English

Code System Code Type Description

SMS_ID

300000041499