About the Target

According to the context information provided, p300 (EP300) plays significant roles in hepatic glucose homeostasis [1]. In the fasting condition, p300 is involved in the phosphorylation of CREB, which leads to increased expression of the FOXO1 gene. Consequently, FOXO1 promotes the expression of PEPCK1 and G6Pase genes, contributing to gluconeogenesis. Conversely, in the feeding condition, p300 binds to the CREB coactivator complex, supporting basal gluconeogenesis and maintaining euglycemia [1].

Furthermore, in prostate cancer (PCa) cells, p300 is implicated in the regulation of PD-L1 (CD274) expression [2]. Acting as a histone acetyltransferase, p300/CBP directly binds to the CD274 promoter, controlling its expression. The secretion of PD-L1, which has immunosuppressive effects and hampers T cell function, is primarily facilitated by exosomes in PCa cells. By inhibiting p300/CBP with A485, the process of PD-L1 secretion can be disrupted, resulting in the reactivation of T cell function for improved tumor attack when combined with anti-PD-L1 antibody treatment [2].

Overall, p300 (EP300) plays a crucial role in hepatic glucose homeostasis by influencing key gene expressions in fasting and feeding conditions. Additionally, in prostate cancer, p300/CBP regulates the expression and secretion of PD-L1, which has implications for T cell function and anti-tumor immune responses [1][2].

Note: If you are interested in the full version of this target analysis report, or if you'd like to learn how our AI-powered BDE-Chem can design therapeutic molecules to interact with the EP300 target at a cost 90% lower than traditional approaches, please feel free to contact us at BD@silexon.ai.

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