Plasma levels of KW-2449 and the metabolite M1. Plasma was obtained 2, 4, 8, and 12 hours after dosing on day 1 and day 14 of cycle 1 of the clinical trial for all patients enrolled. A “composite” drug level was determined by adding the concentration of KW-2449 with the concentration of the metabolite divided by 3.6 ([M1] / 3.6). The 3.6 divisor was derived from the standard curve experiments described in Figure 2. The graphs display the means values of these composite numbers at each of 7 dose levels (25, 50, 100, 200, 300, 400 and 500 mg per day), with error bars representing the standard error of the mean. The dashed line at 500 nM represents the level of drug estimated to be necessary in order to achieve a significant cytotoxic effect via FLT3 inhibition. (A) Day 1. (B) Day 14.