Parameter | vs. Cinacalcet | vs. NPS2143 | ||
---|---|---|---|---|
eq. 5 | eq. 7 | eq. 6 | eq. 8 | |
pEC50 | 3.3 ± 0.01 | 3.3 ± 0.01 | n.d. | n.d. |
pKA [KA (mM)] | n.d. | n.d. | 3.6 ± 0.2 (0.3) | 2.9 ± 0.1 (1.3) |
pKB [KB (µM)] | 6.3 ± 0.04 (0.5) | 5.8 ± 0.1 (1.6) | 6.6 ± 0.04 (0.3) | 7.3 ± 0.1 (0.05) |
Log τA (τA) | n.d. | n.d. | 0.2 ± 0.1 (1.6) | 1.8 ± 0.1 (63) |
Log τB (τB) | n.a. (0) | n.a. (0) | n.a. (0) | n.a. (0) |
Log αβ (αβ) | 0.5 ± 0.01 (3.2) | 1.4 ± 0.1 (25) | −0.2 ± 0.1 (0.6) | −1.7 ± 0.1 (0.02) |
n | 2.8 ± 0.1a | 2.8 ± 0.1a | 12 ± 4.0a | 3.5 ± 0.2a |
Em (% ionomycin) | 79 ± 1.0 | 80 ± 1.0 | 78 ± 1.0 | 80 ± 2 |
Dfd, degrees of freedom denominator; Dfn, degrees of freedom numerator; Em, maximum system response; Log αβ (αβ), modulator cooperativity; Log τA (τA), efficacy; Log τB (τB), modulator efficacy; efficacy; n, transducer or binding slope; n.a., no agonist activity [log τB fixed to −100 (τB 0)]; n.d., not determined; pEC50, potency; pKA (KA), affinity; pKB (KB), modulator affinity .
↵a An F test determined that data were fitted best when the transducer or binding slopes were different from unity. The F data used to test the hypothesis that n differed from 1 were the following: eq. 5 cinacalcet P < 0.0001, F [(Dfn, Dfd) 1249 (1, 2429)]; eq. 5 NPS2143 P < 0.0001, F [(Dfn, Dfd) 1022 (1, 908]; eq. 7 cinacalcet P < 0.0001, F [(Dfn, Dfd) 1241 (1, 2429)]; and eq. 7 NPS2143 P < 0.0001, F [(Dfn, Dfd) 504.5 (1, 907)].