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  • Title: Antiproliferative and protein kinase binding activities of Some N6, 5'-bis-ureido 5'-amino-5'-deoxyadenosine derivatives.
    Author: Peterson MA, Oliveira M, Christiansen MA.
    Journal: Nucleosides Nucleotides Nucleic Acids; 2009 May; 28(5):394-407. PubMed ID: 20183591.
    Abstract:
    Two novel N(6),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 GI(50) values of 1-6 microM 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 > or =30% at 10 microM 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.
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