同义名 :	-
	CAS号 :	2443789-32-8
	货号 :	A1365236
	分子式 :	C23H23FN2O5
	纯度 :	98%
	分子量 :	426.44
	MDL号 :	MFCD31813641
	存储条件：	Pure form Sealed in dry,2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

CBP and p300 are highly homologous coactivators which promote gene transcription by bridging between DNA-binding transcription factors and the basal transcription machinery, by providing a scaffold for integrating transcription factors, and by modifying transcription factors and chromatin through acetylation[2]. CBP/p300-IN-1 is a CBP/EP300 bromodomain (BRD) inhibitor（BDIs）[1]. The presence of amyloid-like aggregates coincides with increased cytotoxicity, and cell viability can be restored upon co-treating cells with small-molecule p300/CBP BDIs, which reflect reduced levels of protein aggregates. p300/CBP BDIs impede aggregation, which coincides with enhanced UPS function and increased cell viability[3]. CBP/EP300 bromodomain inhibition decreases somatic-specific gene expression, histone H3 lysine 27 acetylation (H3K27Ac) and chromatin accessibility at target promoters and enhancers. The master mesenchymal transcription factor PRRX1 is one such functionally important target of CBP/EP300 bromodomain inhibition[4]. In preclinical tumor models, in vivo administration of a CBP/EP300-BRD inhibitor (CBP/EP300-BRDi) alters intratumoral MDSCs and attenuates established tumor growth in immunocompetent tumor-bearing mice, as well as in MDSC-dependent xenograft models. Inhibition of CBP/EP300-BRD redirects tumor-associated MDSCs from a suppressive to an inflammatory phenotype through downregulation of STAT pathway-related genes and inhibition of Arg1 and iNOS. Similarly, CBP/EP300-BRDi decreases differentiation and suppressive function of human MDSCs in vitro[5].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.34mL 0.47mL 0.23mL	11.72mL 2.34mL 1.17mL	23.45mL 4.69mL 2.34mL

参考文献

[1]Xiang Q, et al. Discovery and optimization of 1-(1H-indol-1-yl)ethanone derivatives as CBP/EP300 bromodomain inhibitors for the treatment of castration-resistant prostate cancer. Eur J Med Chem. 2018 Mar 10;147:238-252. [2]R Janknecht. The versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease. Histol Histopathol. 2002 Apr;17(2):657-68. [3] Heidi Olzscha,et al. CBP/p300 Bromodomains Regulate Amyloid-like Protein Aggregation upon Aberrant Lysine Acetylation. Cell Chem Biol. 2017 Jan 19;24(1):9-23. [4] Ayyub Ebrahimi,et al. Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming. Nat Chem Biol. 2019 May;15(5):519-528. [5] Denise E de Almeida Nagata,et al. Regulation of Tumor-Associated Myeloid Cell Activity by CBP/EP300 Bromodomain Modulation of H3K27 Acetylation. Cell Rep. 2019 Apr 2;27(1):269-281.e4.