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

Table 2

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

Compound	Aβ42 IC50 (nM)	Brain/plasma ratio	clogP	LE	LLE	LELP	References
	29		7.5	0.37	0.04	21	[22]
	83	~1	4.8	0.32	2.3	15	[23]
	63		5.2	0.33	2.1	16	[24]
	107		5.4	0.28	1.6	19	[25]
	33		6.6	0.31	0.9	21	[26]
	44		6.4	0.35	0.9	19	[27]
	188	2.9	4.0	0.34	2.7	12	[28]
	16	0.7–1.1	5.2	0.34	2.6	15	[15]

^aLE, LLE, and LELP were calculated using the formulas given in the Methods section. In vitro potency values were taken from the indicated references, except for 3, for which Aβ42 IC₅₀ was determined internally.