Table 2 Binding of MK-1064 for OX1R and OX2R across species relative to other 2-SORAs and MK-6096 and hOX2R binding kinetics.

From: Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man

 

2-SORAs

DORA

MK-1064

2-SORA-18

MK-3697

2-SORA-7

MK-6096

OX 1 R affinity (K i in nM)

 Mouse

1159

98

3951

1693

2.9

 Rat

1069

94

2388

2613

2.5

 Rabbit

2438

241

4740

4394

2.6

 Dog

1300

86

3100

1800

2.7

 Rhesus

815

132

2176

1336

12.5

 Human

1500

100

3500

2800

2.5

OX 2 R affinity (K i in nM) [ fold OX 2 R selectivity]

 Mouse

1.02

0.15

1.47

0.83

0.56

[1136]

[653]

[2688]

[2040]

[5.2]

 Rat

0.83

0.18

1.93

0.22

0.22

[1288]

[522]

[1237]

[11877]

[11.4]

 Rabbit

0.51

0.10

1.01

0.44

0.28

[4780]

[2410]

[4693]

[9986]

[9.3]

 Dog

0.78

0.11

1.10

0.63

0.36

[1667]

[782]

[2818]

[2857]

[7.5]

 Rhesus

0.62

0.11

1.14

0.67

0.44

[1315]

[1200]

[1909]

[1994]

[28.4]

 Human

0.52

0.10

0.97

0.47

0.31

[2885]

[1000]

[3608]

[5957]

[8.1]

hOX 2 R binding kinetics

 Kd (nM)

0.51

ND

1.16

ND

0.34

 T1/2ON (min)

21.1

ND

24.3

ND

62.9

 KON (min−1)

1.19 × 107

 

4.69 × 106

 

9.19 × 106

 T1/2OFF (min)

110

ND

54.4

ND

118.3

 KOFF (mol−1min−1)

6.97 × 10−3

 

1.30 × 10−2

 

1.88 × 10−2

  1. ND, not determined.
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