1. Complete Nek2/CDK2 inhibitory data for synthesised inhibitors
Complete data including compounds referred to, but not shown in the main article.
Note: compounds designated ‘S’ are shown in electronic supplementary information only.
Table S2. Inhibition of CDK2 and Nek2 by 2-arylamino-O6-cyclohexylmethylpurines.
A
B
C
IC50 (µM) or % inhibition
Compound
Substructure
R
Nek2
CDK2
(30 µM ATP) a
(12.5 µM ATP) b
8
A
CONH2
19
0.48
19
B
NO2
>50
1.9
20
A
NO2
>50
0.89
21
B
NH2
6.3
0.22
22
A
NH2
5.9
0.70
30
B
51% at 50 μM
2.2
S27
B
NHCOMe
9.5
0.62
27
A
NHCOMe
8.3
0.88
S28
B
NHCOEt
9.8
0.96
1
S29
B
NHCOiPr
21
6.3
28
B
NHCOtBu
24
9.7
29
B
NHCOPh
36% at 50 μM
2.9
10
A
CONHCH3
15
0.83
11
A
CON(CH3)2
0.62
7.0
14
A
SO2N(CH3)2
40% @ 50 µM
3.5
5.2
5.7
46% @ 50 µM
0.33
S
12
A
13
A
15
C
23
A
24
C
N
S
H2 N
CONHCH3
CO2H
1.3
4.3
0.46
CO2H
0.32
0.99
1.3
O
57% @ 50 µM
32
A
S31
A
4.3
0.47
33
A
3.8
0.73
79% @ 50 µM
0.94
4.1
1.1
N
18
O
34
C
N
H
O
35
C
N
H
2
O
36
C
8.4
2.1
26% @ 50 µM
1.6
N
H
O
37
C
38
C
CON(i-Pr)2
21
3.2
S32
C
CON(Et)2
2.0
0.78
3.1
0.45
53% @ 50 µM
1.3
82% @ 50 µM
0.74
1.3
0.8
6.13
1.6
0.28
1.0
1.0
0.59
29% @ 50 µM
3.7
1.2
0.81
N
O
S33
C
N
O
S34
C
39
C
N
CONH-n-Pr
O
40
C
HO
N
H
O
41
C
N
N
H
N
O
42
C
43
C
N
N
H
O
N
N
H
O
44
C
S35
C
N
H
O
H2N
N
H
3
45
C
0.7
0.86
5.4
2.4
6.9
2.5
O
S36
C
N
O
N
H
O
S37
C
O
N
N
H
S38
C
3.3
0.84
46
C
3.6
2.4
S39
C
1.3
0.66
47
C
Inactive
10
26
C
30% @ 50 µM
1.1
48
C
SO2N(Me)2
0.83
0.77
C
O O
S
N
4.5
0.82
S40
O
4
S41
49
50
C
O O
S
N
74% @ 50 µM
1.1
C
O O
S
N
53% @ 50 µM
1.6
2.6
0.45
20
1.1
1.42
0.53
3.8
1.6
30% @ 100 µM
64
15% @ 50 µM
36
38% @ 100 µM
3.0
9% @ 50 µM
2.4
Inactive
34
O O
S
N
C
HN
S42
O O
S
N
H
C
51
C
S43
C
O O
S
N
H
N
O
S44
S45
52
N
O O
S
N
H
O O
S
N
H
C
O O
S
N
H
C
O O
S
N
H
C
O
O
S46
C
S47
C
O O
S
N
H
O O
S
N
H
5
81% @ 50 µM
0.24
B
6.6
0.37
31
A
3.6
0.38
16
B
2.2
1.1
S23
A
5.9
0.48
17
B
1.1
0.86
S24
B
2.4
0.63
18
B
1.2
0.72
53
C
S30
SO2NH2
All IC50 values are results obtained from n = 3 determinations. aNek2 assay conducted at 30 µM ATP
concentration – full details in reference 21. b CDK assay conducted at 12.5 µM – full details in
reference 19.
6
Table S3. Nek2 and CDK2 inhibition by selected 6-unsubstituted and 6-substituted purines.
Compound
59
R1
OEt
60
R2
IC50 (µM) or % inhibition
Nek2
CDK2
(30 µM ATP) a
(12.5 µM ATP) b
0.89
5.6
4.9
0.41
62
OEt
2.8
5.2
65
H
4.5
30% @ 100 µM
67
H
5.9
>100
S50
1.9
8.6
S51
0.96
2.6
7
69
0.34
5.8
70
0.77
3.0
71
0.24
0.65
72
0.27
2.7
73
3.0
6.9
S52
3.0
13
S53
1.7
7.9
All IC50 values are results obtained from n = 3 determinations. aNek2 assay conducted at 30 µM ATP
concentration – full details in reference 21. b CDK assay conducted at 12.5 µM – full details in in
reference 19.
8