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.

	pKIa	n	konb (× 106)	koffc	Residence timed	n	pKDe
			M−1min−1	min−1	min
[3H]methoxy-PEPy	8.24 ± 0.09f	4	14.2 ± 4.3	0.133 ± 0.006	7.6 ± 0.4	6	8.04
AZD2066	8.53 ± 0.13	3	12.6 ± 1.3	0.045 ± 0.007	26.0 ± 6.2	5	8.50
Basimglurant	9.29 ± 0.06	3	13.6 ± 2.9	0.005 ± 0.002	491 ± 136	8	9.44
Dipraglurant	7.67 ± 0.11	3	33.8 ± 16.0	0.691 ± 0.235	2.2 ± 0.5	6	7.69
F169521	7.21 ± 0.11	3	10.6 ± 3.2	0.471 ± 0.063	2.3 ± 0.4	4	7.35
F1699611	7.58 ± 0.05	3	21.3 ± 7.4	0.496 ± 0.091	2.2 ± 0.4	4	7.63
Mavoglurant	8.10 ± 0.06	3	1.1 ± 0.2	0.006 ± 0.002	478 ± 157	8	8.26
Remeglurant	7.74 ± 0.07	3	4.5 ± 1.0	0.072 ± 0.016	19.9 ± 5.3	7	7.81
(RS)-remeglurant	7.48 ± 0.07	3	2.4 ± 0.5	0.078 ± 0.019	23.1 ± 11.9	5	7.48
STX107	8.32 ± 0.08	3	37.9 ± 6.5	0.166 ± 0.011	6.2 ± 0.4	6	8.35

^aNegative logarithm of the equilibrium dissociation constant.

^bAssociation rate constant.

^cDissociation rate constant.

^dResidence time is defined by 1/k_off, where individual k_off values approached zero for basimglurant and mavoglurant; these were limited to 0.001.

^eNegative logarithm of the equilibrium dissociation constant determined from kinetic parameters (k_off/k_on).

^fpK_D derived from saturation binding paradigm.