Table 4. Sensitivity of recombinant TbDHFR-TS to DHFR and TS inhibitors compared with their human counterparts.

Inhibitor	DHFR Ki, nM		TS Ki, nM
	T. brucei	Human	T. brucei	Human
Methotrexate	0.095 ± 0.006	0.0034a	46,300 ± 4,800	13,000g
Trimetrexate	0.597 ± 0.029	0.040b	Inactive *	—
Pyrimethamine	6.35 ± 0.49	1.2c 120d	Inactive**	—
Trimethoprim	17.6 ± 1.5	200c 1400d	Inactive**	—
Raltitrexed	93.1 ± 7.9	93e	215 ± 18	60e
Pemetrexed	290 ± 20	7.0f	20,500 ± 200	110f
Nolatrexed	348 ± 30	Inactiveh	39.4 ± 4.9	15h
FdUMP	Inactive**	Not reported	13.8 ± 1.3	1.7i

K_i values were determined using spectrophotometric methods. Values represent weighted mean and standard error of three independent determinations.

Human data from:

^a Appleman et al. [45];

^b Jackson et al. [46];

^c Margosiak et al. [47];

^d Chowdhury et al. [48];

^e Jackman et al.[12];

^f Shih et al. [11];

^g Allegra et al. [49];

^h Webber et al. [10];

ⁱ Dolnick and Cheng [32]

Inactive:

* No inhibition at 25 μM;

** No inhibition at 100 μM