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. 2024 Jan 10;67(2):864–884. doi: 10.1021/acs.jmedchem.3c01861

Figure 9.

Figure 9

(a) Overlay of BRD4 bromodomain 1 and bromodomain 2 showing the high degree of sequence and structural similarity between the two domains. BRD4 bromodomain 1 (PDB entry 2OSS) in blue and BRD4 bromodomain 2 (PDB entry 2OUO) in green. (b) Overlay of all 50 BRD4 bromodomain 2 complex structures publicly available at the time this Perspective was written, with the only compound discovered using affinity-mediated selection from a DNA-encoded chemical library shown in blue.109 The DNA-encoded chemical library hit uniquely displaces an otherwise conserved water molecule with its methoxy group. (c) BRD4 inhibitors discovered using DNA-encoded chemistry showing selectivity for bromodomain 2 over bromodomain 1. (d) BRD4 bromodomain 2 in complex with the DEL hit 19 (blue) overlaid with the apo protein (green).109