𝛾-Secretase Modulators: Can We Combine Potency with Safety?

Table 1

Key parameters and efficiency indices of a set of representative acid GSMs.^a

Compound	A𝛽42 IC50 (𝜇M)	Brain/plasma ratio	clogP	LE	LLE	LELP	References
	268	~0.01	3.8	0.28	−0.3	14	[8, 18]
	40	0.03–0.05	5.2	0.29	−0.8	18	[18]
	0.2	0.5–1	8.7	0.28	−2.0	31	[16]
	0.15	~1	5.0	0.27	1.9	18	[19]
	0.32		6.7	0.25	−0.3	26	[20]
	0.6	0.27	3.8	0.25	2.4	15	[21]

^aLE, LLE, and LELP were calculated using the formulas given in the Methods section. In vitro potency values were taken from the indicated references.