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Table 1 Summary of inhibition data obtained for lerisetron, analog 1 and analog 2 on mutant and wildtype receptors. Ki values were calculated from IC50 values as previously described. All data is the result of n > 4 experiments and is expressed as the mean ± SE. The relative change in Ki was calculated as the Ki (mutant) / Ki (wildtype) and indicates the increase in Ki relative to wildtype ± SE. * indicates significant difference in fold change value. Kd values for [3H]granisetron binding to wt and mutant receptors were reproduced from reference 25.

From: Functional group interactions of a 5-HT3R antagonist

Ligand

[3H] Granisetron

Lerisetron

Analog 1

Analog 2

Amino acid

Kd (nM)

Fold change

Ki (nM)

Fold change

Ki (nM)

Fold change

Ki (nM)

Fold change

WT

0.98 ± 0.12

1

0.8 ± 0.19

1

25 ± 3.2

1

320 ± 82

1

W89F

5.7 ± 0.7

5.8 ± 0.7

3.8 ± 0.46

4.8 ± 0.56*

170 ± 54

7.0 ± 3.2*

1600 ± 400

5.1 ± 1.3*

W89Y

18 ± 2.0

18 ± 2.1

2.8 ± 0.14

3.5 ± 0.38*

81 ± 14

3.2 ± 0.6*

2200 ± 520

6.8 ± 1.6*

R91A

4.9 ± 0.7

5 ± 0.8

6.1 ± 1.16

7.6 ± 1.45*

22.7 ± 8

0.9 ± 0.28

180 ± 27

0.56 ± 0.14

Y140A

2.7 ± 0.2

2.8 ± 0.3

2.1 ± 0.33

2.6 ± 0.37

88 ± 45

3.5 ± 1.7

470 ± 210

1.4 ± 0.65

Y142A

4.5 ± 0.5

4.6 ± 0.5

130 ± 28

160 ± 37

170 ± 58

6.8 ± 2.3*

5500 ± 240

17 ± 0.77

Y152A

7.8 ± 1.1

8 ± 1.1

150 ± 36

190 ± 43

2500 ± 400

98 ± 16

13000 ± 4200

40 ± 12