PU139
目录号 : GC63405
PU139 是一种有效的泛组蛋白乙酰转移酶 (HAT) 抑制剂。PU139 阻断 HATs Gcn5、p300/CBP 相关因子 (PCAF)、CBP 和 p300，IC50 分别为 8.39、9.74、2.49 和 5.35 μM。
Cas No.:158093-65-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
PU139 is a potent pan-histone acetyltransferase (HAT) inhibitor. PU139 blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB (cAMP response element-binding) protein (CBP) and p300 with IC50s of 8.39, 9.74, 2.49 and 5.35 μM, respectively[1][2].
PU139 inhibits cell growth with GI50s of <60 μM (A431, A549, A2780, HepG2, SW480, U-87 MG, HCT116 and SK-N-SH and MCF7 cells)[1].PU139 (0-100 μM; 24-72 hours) triggers caspase-independent cell death in the neuroblastoma cell line SK-N-SH[1].
PU139 (25 mg/kg; i.p.) synergizes with Doxorubicin used as a prototypic chemotherapeutic drug in growth inhibition[1].
[1]. Gajer JM, et al. Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo. Oncogenesis. 2015;4(2):e137. Published 2015 Feb 9. [2]. Carneiro VC, et al. Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis. PLoS Pathog. 2014;10(5):e1004116. Published 2014 May 8.
| Cas No. | 158093-65-3 | SDF | |
| 分子式 | C12H7FN2OS | 分子量 | 246.26 |
| 溶解度 | DMSO : 12.5 mg/mL (50.76 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | 4°C, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.0607 mL | 20.3037 mL | 40.6075 mL |
| 5 mM | 0.8121 mL | 4.0607 mL | 8.1215 mL |
| 10 mM | 0.4061 mL | 2.0304 mL | 4.0607 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Investigation of intermolecular interactions and binding mechanism of PU139 and PU141 molecules with p300 HAT enzyme via molecular docking, molecular dynamics simulations and binding free energy analysis
J Biomol Struct Dyn 2023 Mar;41(4):1351-1365.PMID:34974819DOI:10.1080/07391102.2021.2020164.
The p300 histone acetyltransferase (HAT) enzyme acetylates the lysine residue of histone promotes the transcription reaction. The abnormal function of p300 HAT enzyme causes various diseases such as Cancer, Asthma, Alzheimer, Diabetics, and AIDS. In the recent years, several studies have been conducted to design potential drug to inhibit this enzyme. Recently, an in vitro study has been performed on the synthetic molecules PU139 and PU141 to inhibit the p300 HAT enzyme. The present study aims to understand the binding affinity, intermolecular interactions, conformational stability and binding energy of PU139 and PU141 molecules in the active site of p300 HAT enzyme from the in silico studies. The molecular docking and molecular dynamics (MD) simulations were carried out for both ligands with the p300 HAT enzyme. The molecular docking and MD simulations reveals that both molecules forms expected interactions with the catalytic site key residues of p300 enzyme. The MD simulation shows the maximum RMSD value for the PU141 is 2.3 Å, whereas for PU139 is 3.3 Å; these low RMSD values indicate that both molecules are highly stable in the active site of p300. The calculated binding free energy of PU141 (-20.62 kcal/mol) is higher than the molecule PU139 (-17.67 kcal/mol). Among the results, PU141 shows the high binding affinity with p300 while comparing with PU139. The results of this in-silico study coupled with the findings reported in the in vitro study confirm that PU141 may be suitable for clinical study.Communicated by Ramaswamy H. Sarma.
Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo
Oncogenesis 2015 Feb 9;4(2):e137.PMID:25664930DOI:10.1038/oncsis.2014.51.
We have previously described novel histone acetyltransferase (HAT) inhibitors that block neuroblastoma cell growth in vitro. Here we show that two selected pyridoisothiazolone HAT inhibitors, PU139 and PU141, induce cellular histone hypoacetylation and inhibit growth of several neoplastic cell lines originating from different tissues. Broader in vitro selectivity profiling shows that PU139 blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB (cAMP response element-binding) protein (CBP) and p300, whereas PU141 is selective toward CBP and p300. The pan-inhibitor PU139 triggers caspase-independent cell death in cell culture. Both inhibitors block growth of SK-N-SH neuroblastoma xenografts in mice and the PU139 was shown to synergize with doxorubicin in vivo. The latter also reduces histone lysine acetylation in vivo at concentrations that block neoplastic xenograft growth. This is one of the very few reports on hypoacetylating agents with in vivo anticancer activity.
Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis
PLoS Pathog 2014 May 8;10(5):e1004116.PMID:24809504DOI:10.1371/journal.ppat.1004116.
Treatment and control of schistosomiasis relies on the only available drug, praziquantel, and the search for alternative chemotherapeutic agents is therefore urgent. Egg production is required for the transmission and immunopathology of schistosomiasis and females of S. mansoni lay 300 eggs daily. A large fraction of the total mRNA in the mature female worm encodes one eggshell protein, Smp14. We report that the nuclear receptors SmRXR1 and SmNR1 regulate Smp14 transcription through the recruitment of two histone acetyltransferases (HATs), SmGCN5 and SmCBP1. The treatment of HEK293 cells with histone deacetylase (HDAC) inhibitors (NaB or TSA) produced an 8-fold activation of the SmRXR1/SmNR1-mediated Smp14 promoter activity. Incubation with synthetic HAT inhibitors, including PU139, significantly impaired the Smp14 promoter activity in these cells. Worm pairs cultivated in the presence of PU139 exhibited limited expression of Smp14 mRNA and protein. ChIP analysis demonstrated chromatin condensation at the Smp14 promoter site in worms treated with PU139. ChIP also revealed the presence of H3K27me3 and the absence of RNA Pol II at the Smp14 promoter region in the PU139-treated worms. Most significantly, the PU139-mediated inhibition of Smp14 expression resulted in a significant number of abnormal eggs as well as defective eggs within the ootype. In addition, scanning electron microscopy revealed structural defects and unformed eggshells, and vitelline cell leakage was apparent. The dsRNAi-targeting of SmGCN5 or SmCBP1 significantly decreased Smp14 transcription and protein synthesis, which compromised the reproductive system of mature female worms, egg-laying and egg morphology. Our data strongly suggest that the inhibition of Smp14 expression targeting SmGCN5 and/or SmCBP1 represents a novel and effective strategy to control S. mansoni egg development.
Identification of histone acetyltransferase genes responsible for cannabinoid synthesis in hemp
Chin Med 2023 Feb 13;18(1):16.PMID:36782242DOI:10.1186/s13020-023-00720-0.
Background: Histone acetyltransferases (HATs) play an important role in plant growth and development, stress response, and regulation of secondary metabolite biosynthesis. Hemp (Cannabis sativa L.) is famous for its high industrial, nutritional, and medicinal value. It contains non-psychoactive cannabinoid cannabidiol (CBD) and cannabinol (CBG), which play important roles as anti-inflammatory and anti-anxiety. At present, the involvement of HATs in the regulation of cannabinoid CBD and CBG synthesis has not been clarified. Methods: The members of HAT genes family in hemp were systematically analyzed by bioinformatics analysis. In addition, the expression level of HATs and the level of histone acetylation modification were analyzed based on transcriptome data and protein modification data. Real-time quantitative PCR was used to verify the changes in gene expression levels after inhibitor treatment. The changes of CBD and CBG contents after inhibitor treatment were verified by HPLC-MS analysis. Results: Here, 11 HAT genes were identified in the hemp genome. Phylogenetic analysis showed that hemp HAT family genes can be divided into six groups. Cannabinoid synthesis genes exhibited spatiotemporal specificity, and histones were acetylated in different inflorescence developmental stages. The expression of cannabinoid synthesis genes was inhibited and the content of CBD and CBG declined by 10% to 55% in the samples treated by HAT inhibitor (PU139). Results indicated that CsHAT genes may regulate cannabinoid synthesis through altering histone acetylation. Conclusions: Our study provides genetic information of HATs responsible for cannabinoid synthesis, and offers a new approach for increasing the content of cannabinoid in hemp.