Table 2. Hemoglobin-modification, change in oxygen equilibrium and antisickling studies on test compounds using human sickle blood.

All studies were conducted with SS cell suspensions (20% hematocrit) incubated with 0.5, 1, 1.5 and 2 mM of each test compound. The results are the mean values ± SD for five individual replicate experiments. The final concentration of DMSO was <2% in all samples, including in control samples.

	Modified Hb† (%)				ΔP 50 ‡ (%)				Sickling inhibition§ (%)
	0.5 mM	1 mM	1.5 mM	2 mM	0.5 mM	1 mM	1.5 mM	2 mM	0.5 mM	1 mM	1.5 mM	2 mM
TD8	13.1 ± 2.9	19.7 ± 7.2	18.0 ± 2.6	29.3 ± 12.7	7.1 ± 4.4	16.4 ± 11.5	13.2 ± 3.5	23.3 ± 14.5	4.7 ± 4.4	6.5 ± 7.6	9.2 ± 6.8	9.9 ± 6.2
TD9	17.0 ± 3.5	27.8 ± 3.8	35.2 ± 4.7	43.9 ± 5.5	7.9 ± 2.7	18.4 ± 4.9	29.1 ± 9.3	35.2 ± 2.0	8.0 ± 7.8	10.6 ± 7.3	19.6 ± 5.5	26.6 ± 9.5
TD7	25.9 ± 7.6	45.3 ± 11.6	59.5 ± 10.7	74.0 ± 8.0	10.0 ± 2.9	27.6 ± 11.7	29.3 ± 7.2	48.2 ± 9.5	16.4 ± 6.3	29.1 ± 6.1	57.5 ± 10.9	84.7 ± 13.6
SAJ310	30.9 ± 9.5	54.0 ± 13.4	75.2 ± 7.2	83.3 ± 6.7	20.8 ± 10.9	35.7 ± 12.1	37.5 ± 6.7	58.1 ± 12.6	19.2 ± 4.8	47.7 ± 10.8	92.4 ± 5.9	97.3 ± 0.6

^†Hb S adduct values obtained from HPLC elution patterns of individual hemolysates after incubation of compounds with SS cells.

^‡ P ₅₀ is the oxygen pressure at which the hemolysates are 50% saturated with oxygen. ΔP ₅₀ was determined as ΔP ₅₀ (%) = (P ₅₀ of lysates from untreated cells − P ₅₀ of lysates from treated cells × 100)/(P ₅₀ of lysates from untreated cells).

^§Antisickling studies with SS cells were conducted under hypoxia (4% oxygen/96% nitrogen).