Protein lysine acetyltransferase CBP/p300: A promising target for small molecules in cancer treatment - 04/02/24
Abstract |
CBP and p300 are homologous proteins exhibiting remarkable structural and functional similarity. Both proteins function as acetyltransferase and coactivator, underscoring their significant roles in cellular processes. The function of histone acetyltransferases is to facilitate the release of DNA from nucleosomes and act as transcriptional co-activators to promote gene transcription. Transcription factors recruit CBP/p300 by co-condensation and induce transcriptional bursting. Disruption of CBP or p300 functions is associated with different diseases, especially cancer, which can result from either loss of function or gain of function. CBP and p300 are multidomain proteins containing HAT (histone acetyltransferase) and BRD (bromodomain) domains, which perform acetyltransferase activity and maintenance of HAT signaling, respectively. Inhibitors targeting HAT and BRD have been explored for decades, and some BRD inhibitors have been evaluated in clinical trials for treating hematologic malignancies or advanced solid tumors. Here, we review the development and application of CBP/p300 inhibitors. Several inhibitors have been evaluated in vivo, exhibiting notable potency but limited selectivity. Exploring these inhibitors emphasizes the promise of targeting CBP and p300 with small molecules in cancer therapy.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | CBP/p300 dysregulation correlates with diverse diseases, especially cancer, arising from loss or gain of function mutations. |
• | Inhibitors designed to target the HAT and bromodomain BRDdomains of CBP/p300 have undergone significant development. |
• | In vivo evaluation of some inhibitors shows considerable potency, but achieving specificity remains a persistent challenge. |
• | Clinical trial studies highlight the potential of CBP/p300 as promising targets for small molecule-based cancer therapeies. |
Keywords : CBP/p300, Transcription regulator, Bromodomain inhibitors, HAT inhibitors, Cancer treatment
Plan
Vol 171
Article 116130- février 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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