Operational model parameters and fold shift values for NCFP and CPPHA modulation of intracellular Ca2+ mobilization
Data represent the mean ± S.E.M. from a minimum of three individual experiments conducted in duplicate.
| Parameter | Wild-type-mGlu5 | F585I-mGlu5 | ||
|---|---|---|---|---|
| NCFP | CPPHA | NCFP | CPPHA | |
| pKBa | 5.56 ± 0.13 | 6.09 ± 0.09d | ND | ND |
| Logβb | 0.99 ± 0.05 | 0.59 ± 0.08d | ND | ND |
| Fold shift (max)c | 7.7 ± 0.1 | 5.9 ± 1.6 | ND | ND |
| Fold shift (3µM)c | 5.9 ± 0.1 | 4.0 ± 0.7 | 1.6 ± 0.1* | 1.3 ± 0.1* |
CPPHA, N-(4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl)-2-hydroxybenzamide; mGlu, metabotropic glutamate receptor; NCFP, N-(4-chloro-2-((4-fluoro-1,3-dioxoisoindolin-2-yl)methyl)phenyl)picolinamide; ND, not determined; PkB, protein kinase B.
↵a Negative logarithm of the allosteric modulator dissociation constant.
↵b Negative logarithm of the efficacy cooperativity factor.
↵c Fold shift values were determined for the maximum fold shift determined for multiple concentrations or at a single (3 µM) concentration.
↵d Operational model parameters were previously reported in Gregory et al., 2012.ND values not determined.
↵* Significantly different (P < 0.05) to wild-type value.