Here, we demonstrate the affinity-mediated selection of DNA-encoded chemical libraries as a discovery methodology for small-molecule binders of the c-myc promoter and demonstrate that these compounds bind their targets using Surface Plasmon Resonance (SPR), a homogeneous solution-phase PCR-stop assay, and we also indicate target engagement in Burkitt lymphoma cell line RA-1 RAMOS, ATCC® CRL-1596 [19] by observing effects upon the expression of c-myc under the control of a G-quartet-containing promoter. The gene discussed is MYC; the disease is Burkitt lymphoma.