Table 2 Structure and activity for analogs of 3.

From: Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions

 

 

EC50 (μM)

EC50 (μM)

EC50 (μM)

EC50 (μM)

EC50 (μM)

m = 1

R = Me

pos

X = F

pos

Y = H

38 Z = NMe

Inactive

11n = 0

Inactive

18

(a)

~ 30.2 ± 12.2a

24

o

5.0 ± 0.8

33 X = Cl

5.7 ± 1.1

39 Z = CH2

14.9 ± 2.1

12n = 1

Inactive

19

(b)

Inactive

25

m

10.8 ± 1.4

34 X = OH

Inactive

3n = 2

9.3 ± 0.7

20

(c)

Inactive

26

p

6.4 ± 0.4

35 X = Br

Aggregated

13n = 3

15.1 ± 3.3

m = 2

R = F

pos

X = CF3

pos

X = H, Y = OH

14n = 0

Inactive

21

(a)

16.1 ± 2.2

27

o

5.2 ± 1.3

36 (S)

11.4 ± 4.4

15n = 1

Inactive

22

(b)

9.3 ± 1.5

28

m

7.3 ± 1.0

37 (R)

11.4 ± 6.1

16n = 2

Inactive

23

(c)

12.9 ± 3.0

29

p

8.4 ± 0.9

17n = 3

72.5 ± 24.4

 

X = OCH2Ph

pos

 

30

o

7.0 ± 0.4

 

31

m

3.7 ± 0.5

 

32

p

2.3 ± 0.4

  1. All compounds were titrated on 2 μM 14-3-3β and 100 nM fluorescently-labeled ChREBP peptide and EC50 values were calculated from the resulting dose–response fluorescence anisotropy curves (Supplementary Fig. 10). Data represent mean ± SEM, n = 3 replicates. Source data are provided as a Source data file.
  2. aNo reliable fit.
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