. Author manuscript; available in PMC: 2012 Oct 13.

Published in final edited form as: J Med Chem. 2011 Sep 16;54(19):6919–6935. doi: 10.1021/jm2008985

Table 3.

Inhibition of PAD isozymes by haloacetamidine-based inhibitors.

Compound	Isozyme	IC₅₀^a (μM)	k_inact (min⁻¹)	K_I (μM)	k_inact/K_I (M⁻¹min⁻¹)
F-amidine	PAD1	29 ± 1.32	0.30 ± 0.03	110 ± 40	2800
	PAD2	51 ± 8.96	ND^b	ND^b	380
	PAD3	367 ± 189	0.05 ± 0.01	293 ± 193	170
	PAD4	22 ± 2.10	1.0 ± 0.1	330 ± 90	3000

Cl-amidine	PAD1	0.8 ± 0.3	2.3 ± 0.1	62 ± 11	37000
	PAD2	17 ± 3.1	ND^b	ND^b	1200
	PAD3	6 ± 1.0	0.056 ± 0.005	28 ± 7.3	2000
	PAD4	5.9 ± 0.3	2.4 ± 0.2	180 ± 33	13000

o-F-amidine	PAD1	1.4 ± 0.41	1.7 ±0.1	9.4 ± 1.8	180900
	PAD2	≥ 50	ND^b	ND^b	7500
	PAD3	34 ± 31.9	ND^b	ND^b	6700
	PAD4	1.9 ± 0.21	0.5 ± 0.17	16 ± 9	32500

o-Cl-amidine	PAD1	0.84 ± 0.12	ND^a	ND^a	106400
	PAD2	6.2 ± 0.7	ND^a	ND^a	14100
	PAD3	0.69 ± 0.34	0.3 ±0.06	29 ± 12	10345
	PAD4	2.2 ± 0.31	0.5 ± 0.11	13 ± 5.2	38000

Given that these compounds are time-dependent irreversible inactivators, these IC₅₀ values should be considered apparent measures of affinity.

ND = Not determinable. Values for k_inact and K_I could not be determined because saturation was not observed in the plots of k_obs versus inactivator concentration.

k_inact/K_I values were determined from linear fits of the data.