 SCIO-469 belongs to a new class of treatment that inhibits p38 MAP kinase. p38 MAPK activation controls the production of TNF-a, VEGF, and IL-1b. As an inhibitor of p38 MAPK, SCIO-469 blocks the synthesis of these molecules, as well as TNF-a activity. This randomized, open-label, modified dose-ascension study is designed to assess the safety, tolerability, and efficacy of oral SCIO-469 in the treatment of patients with MDS. This patient group was selected because of the inhibitory effect of SCIO-469 on the expression and activity of cytokines that play a role in the progression of MDS. The treatment arms will be 30, 60 , 90, or 120 mg tid with 15 subjects per arm total of 60 subjects and each arm may expand to 25 subjects per arm maximum total of 100 subjects. Initially, subjects will be randomly assigned to one of the lowest two treatment arms 30 mg tid or 60 mg tid. When 6 subjects per arm at least 12 subjects total have received study drug for at least 4 weeks, predefined criteria will be used to determine whether to open randomization into the third arm i.e., 90 mg tid. The criteria will be based on the number of subjects who have had to suspend study drug due to drug-related toxicity. The 120-mg tid arm will be open for enrollment after 15 subjects have been enrolled into each of the first three treatment arms; the decision to open enrollment will be similar to the criteria used to open the third arm. Subjects will be evaluated at least monthly for safety and some efficacy measurements AE reporting, safety labs and vitals. Subjects will receive study drug for 16 weeks. Subjects who demonstrate hematologic improvement erythroid, platelet, or neutrophil response by IWG criteria at week 16 will be eligible to continue treatment at the same dose of study drug for up to 36 additional weeks 52 weeks of total drug exposure. Subjects who do not meet the IWG criteria for hematologic improvement at week 16 but who, in the judgment of the investigator, experience clinical benefit may also receive up to 36 additional weeks of treatment. The same judgments for treatment extensions of additional 26 weeks in responding subjects will be made at 52 weeks and 78 weeks; maximum total drug exposure will be 104 weeks. All subjects will be followed for 4 weeks after the last study drug treatment for safety assessments or until resolution of Grade 3 or greater treatment-related toxicity as defined by NCI CTCAE v. 3.0. 