Schild constants for antagonism of [MePhe7]NKB-induced accumulation of [3H]IP by Me-talnetant and osanetant in CHO cells expressing transiently the WT and mutated hNK3Rs
The pA2 and Schild slope values of Me-talnetant and osanetant at the WT and mutated hNK3Rs were determined from NKB CRCs in the absence and presence of various concentrations of antagonist and Schild plot analyses shown in Fig. 5.
hNK3R | Position in the 7TMD | Me-Talnetant | Osanetant | ||||
|---|---|---|---|---|---|---|---|
| pA2 | Schild Slope | pA2 | Schild Slope | ||||
| WT | 8.14 | 0.81 | 7.47 | 1.80 | |||
| V95A | 1.42 | 7.88 | 1.28 | 7.46 | 1.85 | ||
| V95L | 1.42 | 7.59 | 1.70 | 7.24 | 1.70 | ||
| V95I/A99S | 1.42, 1.46 | 7.53 | 1.37 | 7.05 | 1.43 | ||
| M134A | 2.53 | Inactive | Inactive | ||||
| N138A | 2.57 | NKB inactive | NKB inactive | ||||
| T139A | 2.58 | 8.45 | 0.86 | 7.66 | 2.11 | ||
| V95L/T139A | 1.42, 2.58 | 7.52 | 1.04 | 7.18 | 1.85 | ||
| N142A | 2.61 | 8.76 | 1.15 | Inactive | |||
| V169M | 3.36 | Inactive | Inactive | ||||
| L232A | 45.49 | 8.19 | 1.20 | 7.42 | 1.82 | ||
| Y315F | 6.51 | 8.05 | 1.50 | 7.08 | 0.83 | ||
| S341A | 7.38 | 7.79 | 1.64 | 7.28 | 1.56 | ||
| F342A | 7.39 | Inactive | 6.86 | 0.86 | |||
| F342M | 7.39 | Inactive | Inactive | ||||
| S341I/F342M | 7.38, 7.39 | Inactive | Inactive | ||||
| M346A | 7.43 | 8.07 | 1.12 | 7.48 | 1.83 | ||
| S348A | 7.45 | 8.08 | 1.19 | 7.46 | 1.79 | ||