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7300664 
Journal Article 
Gold-Based Pharmacophore Inhibits Intracellular MYC Protein 
Awuah, SG; Ofori, S; Gukathasan, S 
2020 
Yes 
Chemistry: A European Journal
ISSN: 0947-6539
EISSN: 1521-3765 
English 
33275307 
Direct targeting of intrinsically disordered proteins, including MYC by small-molecules for biomedical applications will resolve a longstanding issue in chemical biology and medicine. Thus, we developed gold-based small-molecule MYC reagents that engage MYC inside cells and modulate MYC transcriptional activity. Lead compounds comprise an affinity ligand and a gold(I) or gold(III) warhead capable of protein chemical modification. Cell-based MYC target engagement studies via CETSA and co-immunoprecipitation reveal specific interaction of compounds with MYC in cells. The lead gold(I) reagent, 1, demonstrates superior cell-killing potential (up to 35-fold) in a MYC-dependent manner when compared to 10058-F4 in cells including, the TNBC, MDA-MB-231. Subsequently, 1suppresses MYC transcription factor activity via functional colorimetric assays, and gene-profiling using whole-cell transcriptomics reveals significant modulation of MYC target genes by 1. These findings point to metal-mediated ligand affinity chemistry (MLAC) based on gold as a promising strategy to develop chemical probes and anticancer therapeutics targeting MYC.