TABLE 1

mGlu₅ NAM inhibitor properties

cLogP, partition coefficient; Fup, free fraction in plasma; t_1/2, half life; N/A, not available; Fubr, free fraction in brain

Identifier		Dipraglurant	Mavoglurant	Basimglurant	HTL0014242
Structure
cLogP		2.58	3.16	4.71	3.04
mGlu₅ pK_i (means ± S.D.)	Human	6.98 ± 0.24	7.95 ± 0.24	9.25 ± 0.40	9.30 ± 0.24
	Monkey	N/A	N/A	N/A	8.88 (n = 2) (8.71–9.05)
	Rat	7.21 (n = 2) (7.20–7.22)	8.07 ± 0.16	8.93 (n = 2) (8.81–9.06)	9.19 ± 0.11
	Mouse	7.13 ± 0.11	7.89 ± 0.42	N/A	9.29 ± 0.18
Human plasma t_1/2 (h)		0.68–0.75^a	12 day	49–107^b	N/A
Rat	Fup	0.037	0.15	0.021^c	0.0028
	Fubr	0.13^d	0.03^d	N/A	0.0019
	Kp brain/plasma	0.11	1.6	1.7^c	1.9
	Kpuu	0.39	0.32	1.0^c	1.3

↵^a Tison et al. (2016).
↵^b Cosson et al. (2018).
↵^c Cited Fup and Kpuu assumed 1 based on cited good brain penetration (Lindemann et al., 2015).
↵^d Based on [CSF]/[total brain].
^e Walles et al. (2013).