TABLE 3.

Phe-based derivatives that induced Ca²⁺ mobilization in human neutrophils and FPR-transfected HL-60 cells

The EC₅₀ values are presented as the mean ± S.D. of three independent experiments, in which median effective concentration values (EC₅₀) were determined by nonlinear regression analysis of the dose-response curves (five to six points) generated using GraphPad Prism 5 with 95% confidence interval (P < 0.05). Efficacy is expressed as percentage of the response induced by 5 nM fMLF (FPR1) or 5 nM WKYMVm (FPR2 and FPR3).

Compound	R1	R2	Enan-tiomer	Ca2+ Mobilization, EC50, and Efficacy
				Neutrophils	FPR1	FPR2	FPR3
				μM (%)
AG-10/4	Br		S	3.2 ± 0.6 (115)	4.5 ± 1.1 (90)	0.14 ± 0.05 (100)	11.5 ± 2.8 (55)
AG-10/5	Br		S	1.2 ± 0.3 (140)	1.8 ± 0.5 (130)	0.04 ± 0.02 (115)	6.5 ± 1.7 (85)
AG-10/6	Cl		S	0.5 ± 0.2 (140)	2.9 ± 0.7 (100)	0.05 ± 0.01 (95)	3.1 ± 0.8 (65)
AG-10/7	S-CH3		S	6.6 ± 1.4 (50)	6.0 ± 1.4 (45)	0.3 ± 0.08 (75)	N.A.
AG-10/8	Br		S	0.7 ± 0.2 (145)	0.3 ± 0.08 (135)	0.004 ± 0.002 (115)	0.1 ± 0.03 (90)
AG-10/9	Br		S	0.5 ± 0.1 (110)	0.08 ± 0.02 (100)	0.007 ± 0.003 (100)	0.5 ± 0.1 (50)
AG-10/10	Br		S	4.4 ± 1.2 (85)	N.A.	0.16 ± 0.04 (85)	N.A.
AG-10/11	Br		R/S	9.7 ± 0.2 (90)	6.7 ± 1.6 (75)	0.25 ± 0.06 (55)	N.A.
AG-10/12	Cl		S	10.5 ± 2.6 (100)	4.2 ± 0.9 (85)	0.7 ± 0.3 (55)	N.A.
AG-10/13	CH2CH3		S	10.8 ± 2.2 (110)	3.1 ± 0.7 (105)	1.6 ± 0.3 (75)	N.A.

N.A., nonactive compound (cell activation was <30% of control level over a concentration range of 0–40 μM).

*Location of the chiral center.