Table 6.
Quantitative Determination of Protein:ligand Binding of Compound 2 Analogs to FGF14 and Nav1.6 by SPR.
| Compound | FGF14 | Nav1.6 C-terminal tail | ||||
|---|---|---|---|---|---|---|
| KD* (μM) |
kon (M−1 s−1) |
koff (s−1) |
KD* (μM) |
kon (M−1 s−1) |
koff (s−1) |
|
| 19k | ND | ND | ND | > 200 | 2.57 × 105 | 4.49 × 10−3 |
| 19e | 188.9 ± 3.7 | 4.61 × 102 | 9.91 × 10−4 | ND | ND | ND |
| 21a | 4.05 ± 0.17 | 4.66 × 103 | 9.33 × 10−3 | 16.43 ± 2.05 | 6.23 × 104 | 3.57 × 10−3 |
| 23a | 1.31 ± 0.37 | 1.79 × 104 | 9.32 × 10−3 | > 200 | 6.16 × 106 | 2.73 × 10−3 |
| 23b | 14.72 ± 1.40 | 2.58 × 104 | 2.69 × 10−7 | > 200 | 1.26 × 105 | 1.45 × 10−3 |
| 23d | 6.94 ± 1.08 | 1.62 × 103 | 5.80 × 10−3 | > 200 | 8.29 × 105 | 7.94 × 10−3 |
| 23e | 7.02 ± 1.20 | 7.35 × 103 | 1.39 × 10−2 | > 200 | 7.16 × 105 | 1.70 × 10−4 |
| 23f | 9.47 ± 1.22 | 2.17 × 102 | 2.05 × 10−2 | 67.34 ± 7.3 | 2.64 × 103 | 1.22 × 10−2 |
| 23g | 11.39 ± 2.15 | 2.89 × 102 | 2.04 × 10−2 | 90.14 ± 10.1 | 3.40 × 102 | 4.92 × 10−2 |
The equilibrium dissociation constants (KD) were calculated using data represented in Figure 6. The KD shown for each protein:ligand interaction is an average of the values calculated using the simplest Langmuir 1:1 interaction model (KD = koff/kon) and the steady-state saturation model. ND, non-determinable.