Here, we developed a prodrug for acute myelogenous leukemia (AML) which could overcome the disadvantage of cytarabine such as short plasma half-life and rapid deamination to its inactive metabolite. The new drug-fatty acyl conjugate (Ara-R-Ara) has been synthesized from the hydrophilic anticancer drug cytarabine and hydrophobic fatty acyl suberoyl chloride via a hydrolyzable amido linkage. Suberoyl chloride has been conjugated to cytarabine to protect the NH₂ group from the enzymatic attachment to exhibit a longer blood retention half-life compared with the free drugs. A higher membrane permeability of Ara-R-Ara was obtained compared with pure cytarabine, about 15.4 times the pure drug sample in PAMPA permeability studies. In vitro cytotoxicity results showed that the new prodrug had a much lower IC₅₀ and a higher cell inhibition rate compared with the pure cytarabine for HL60 and K562 cells, indicating its effective therapy for leukemic cells.