Table 3. Pharmacokinetic Properties of Selected PTR1 Inhibitors^a.

	TbPTR1	T. b. brucei HMI-9	T. b. brucei CMM	HEK	Cli	plasma bind	t1/2	clogP	LE PTR1	LE CMM
	Kiapp μM	IC50 μM	IC50 μM	IC50 μM	mL/min/g	fu	min
20	0.19	0.65			5.6			3.35	0.4
29b	0.48	14.5			1.7			1.84	0.48
34a	1.17	0.640	0.407		1.17	0.029	∼130	2.75	0.35	0.38
34c	0.50	0.738	0.614	>200	0.17	0.017		2.90	0.36	0.35
34i	0.95	0.396	0.135	33.2	2.5			3.58	0.33	0.37
34l	0.47	1.405	0.767	57.7	<0.5			3.26	0.35	0.33
35a	0.59	2.247	0.583	62.9	5.26	0.035	∼100	3.41	0.37	0.37
35b	0.24	0.321	0.082	49.2	1.90	0.011	>500	3.57	0.38	0.4

^aBlank cells imply not tested in relevant assay. K_i^app is the apparent dissociation constant for the enzyme inhibitor complex, before correction for the inhibition modality-specific influence of substrate concentration relative to K_m. As the inhibitors compete for binding with the pterin substrate, K_i can be calculated according to the equation K_i^app=K_i /(1 + S × K_m^–1), where S and K_m refer to the pterin substrate. K_i^app and IC₅₀ values refer to the data presented in Tables 1 and 2. Cli is the clearance in vivo. fu is the fraction unbound by plasma. t_1/2 is the half-life of the compound. clogP and ligand efficiency (LE) were obtained using Pipeline Pilot (Accelrys Inc).