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A rationally designed dual PI3-kinase (PI3K) and BET-inhibitory chimeric small molecule demonstrates potent anti-neoplastic activity versus MYC-driven haematological cancers in vivo

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE188443 | GEO | 2023/08/14

REPOSITORIES: GEO

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A rationally designed dual PI3-kinase (PI3K) and BET-inhibitory chimeric small molecule demonstrates potent anti-neoplastic activity versus MYC-driven haematological cancers in vivo [ChIP-seq]

Project description:We hypothesised that PI3K and BET inhibition would synergise in the context of MYC-dysregulation and overcome resistance to single-target inhibition. We then synthesised a series of chimeric molecules linking BET- and PI3K-selective pharmacophores, including our lead molecule, 18D(S). RNA-Seq profiling following acute 18D(S) treatment demonstrated robust transcriptional modulation with concomitant BET and PI3K inhibitory signatures. Our data provides proof-of-concept for the design of potent PI3K- and BET-inhibitors, providing ‘synergy in a single molecule’.

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