TABLE 1

Affinity estimates and kinetic binding parameters for mGlu5 NAMs based on inhibition of [3H]methoxy-PEPy binding

Data are represented as means ± S.E.M. from indicated number (n) of independent experiments performed in duplicate.

pKIankonb (× 106)koffcResidence timednpKDe
M−1min−1min−1min
[3H]methoxy-PEPy8.24 ± 0.09f414.2 ± 4.30.133 ± 0.0067.6 ± 0.468.04
AZD20668.53 ± 0.13312.6 ± 1.30.045 ± 0.00726.0 ± 6.258.50
Basimglurant9.29 ± 0.06313.6 ± 2.90.005 ± 0.002491 ± 13689.44
Dipraglurant7.67 ± 0.11333.8 ± 16.00.691 ± 0.2352.2 ± 0.567.69
F1695217.21 ± 0.11310.6 ± 3.20.471 ± 0.0632.3 ± 0.447.35
F16996117.58 ± 0.05321.3 ± 7.40.496 ± 0.0912.2 ± 0.447.63
Mavoglurant8.10 ± 0.0631.1 ± 0.20.006 ± 0.002478 ± 15788.26
Remeglurant7.74 ± 0.0734.5 ± 1.00.072 ± 0.01619.9 ± 5.377.81
(RS)-remeglurant7.48 ± 0.0732.4 ± 0.50.078 ± 0.01923.1 ± 11.957.48
STX1078.32 ± 0.08337.9 ± 6.50.166 ± 0.0116.2 ± 0.468.35
  • a Negative logarithm of the equilibrium dissociation constant.

  • b Association rate constant.

  • c Dissociation rate constant.

  • d Residence time is defined by 1/koff, where individual koff values approached zero for basimglurant and mavoglurant; these were limited to 0.001.

  • e Negative logarithm of the equilibrium dissociation constant determined from kinetic parameters (koff/kon).

  • f pKD derived from saturation binding paradigm.