Two novel N6,5′-bis-ureido 5′-amino-5′-deoxyadenosine derivatives are shown to inhibit tumor cell growth in the NCI 60 human tumor cell panel. Compounds 2c and 2d exhibited GI50 values of 1–6 μM in 35 and 14 cell lines, respectively. Compound 2c was shown to selectively inhibit binding of protein kinases to immobilized ATP-binding site ligands via a competitive binding assay (11 of 353 protein kinases inhibited by ≥30% at 10 μM compound concentration). Enzyme inhibition assays revealed modest inhibition for PAK4 and FMS (21 and 17%, respectively). A brief SAR study suggests that a 2′-O-TBDMS is necessary for antiproliferative activity.