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Inhibition of Tdp1 by tyrphostin derivatives. (A) Schematic representation of the Tdp1 biochemical gel-based assay. Tdp1 hydrolyzes the 3′-phosphotyrosine bond and converts the N14Y DNA substrate to a 3′-phosphate oligonucleotide product (N14P); (B) representative gel demonstrating concentration-dependent inhibition of Tdp1 by compounds 8 and 9; (C) representative compounds. The pharmacophore of lead compound 8 comprises two domains: the functional head domain and the aromatic moiety.
