Psammaplin A
目录号 : GC60310
PsammaplinA是一种海洋代谢产物，是HDAC和DNA甲基转移酶(DNAmethyltransferases)的有效抑制剂。PsammaplinA是一种高效的选择性HDAC1抑制剂，IC50为0.9nM，对HDAC1的选择性是DAC6的360倍，对HDAC7和HDAC8的效力低1000倍以上。PsammaplinA对革兰氏阳性细菌(Gram-positivebacteria)具有抗菌作用，并抑制DNA合成和DNA促旋酶(DNAgyrase)活性。抗肿瘤活性。
Cas No.:110659-91-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >96.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Psammaplin A, a marine metabolite, is a potent inhibitor of HDAC and DNA methyltransferases. Psammaplin A ia a highly potent and selective DAC1 inhibitor with an IC50 of 0.9 nM. Psammaplin A possess the antimicrobial effect on the Gram-positive bacteria and inhibits DNA synthesis and DNA gyrase activity. Antitumor Activity[1][2].
[1]. Matthias G J Baud, et al. Defining the Mechanism of Action and Enzymatic Selectivity of Psammaplin A Against Its Epigenetic Targets. J Med Chem. 2012 Feb 23;55(4):1731-50. [2]. Psammaplin A, a Natural Bromotyrosine Derivative From a Sponge, Possesses the
| Cas No. | 110659-91-1 | SDF | |
| Canonical SMILES | O=C(NCCSSCCNC(/C(CC1=CC(Br)=C(O)C=C1)=N/O)=O)/C(CC2=CC(Br)=C(O)C=C2)=N/O | ||
| 分子式 | C22H24Br2N4O6S2 | 分子量 | 664.39 |
| 溶解度 | 储存条件 | 4°C, stored under nitrogen | |
| 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 | 1.5051 mL | 7.5257 mL | 15.0514 mL |
| 5 mM | 0.301 mL | 1.5051 mL | 3.0103 mL |
| 10 mM | 0.1505 mL | 0.7526 mL | 1.5051 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。
Marine-Derived Natural Lead Compound Disulfide-Linked Dimer Psammaplin A: Biological Activity and Structural Modification
Mar Drugs 2019 Jun 27;17(7):384.PMID:31252563DOI:10.3390/md17070384.
Marine natural products are considered to be valuable resources that are furnished with diverse chemical structures and various bioactivities. To date, there are seven compounds derived from marine natural products which have been approved as therapeutic drugs by the U.S. Food and Drug Administration. Numerous bromotyrosine derivatives have been isolated as a type of marine natural products. Among them, Psammaplin A, including the oxime groups and carbon-sulfur bonds, was the first identified symmetrical bromotyrosine-derived disulfide dimer. It has been found to have a broad bioactive spectrum, especially in terms of antimicrobial and antiproliferative activities. The highest potential indole-derived Psammaplin A derivative, UVI5008, is used as an epigenetic modulator with multiple enzyme inhibitory activities. Inspired by these reasons, Psammaplin A has gradually become a research focus for pharmacologists and chemists. To the best of our knowledge, there is no systematic review about the biological activity and structural modification of Psammaplin A. In this review, the pharmacological effects, total synthesis, and synthesized derivatives of Psammaplin A are summarized.
Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives
Bioorg Med Chem 2009 Mar 15;17(6):2189-98.PMID:19022675DOI:10.1016/j.bmc.2008.10.077.
The Wnt signaling pathway regulates cell growth and development in metazoans, and is therefore of interest for drug discovery. By screening a library of 5808 pre-fractionated marine extracts in a cell-based Wnt signaling assay, several signaling activators and inhibitors were observed. LCMS-based fractionation rapidly identified an active compound from Pseudoceratina purpurea as Psammaplin A, a known HDAC inhibitor. Other HDAC inhibitors similarly activated signaling in this assay, indicating HDAC inhibitors will be identified through many cell-based reporter assays. In a large scale analysis of P. purpurea, three previously undescribed bromotyrosine based natural products were identified; the structure of one of these was confirmed by synthesis. Additionally, three other derivatives of Psammaplin A were prepared: a mixed disulfide and two sulfinate esters. Finally, evidence to support a structural reassignment of psammaplin I from a sulfone to the isomeric sulfinate ester is presented.
Cytotoxicity of Psammaplin A from a two-sponge association may correlate with the inhibition of DNA replication
BMC Cancer 2004 Sep 30;4:70.PMID:15456519DOI:10.1186/1471-2407-4-70.
Background: SV40 DNA replication system is a very useful tool to understand the mechanism of replication, which is a tightly regulated process. Many environmental and cellular factors can induce cell cycle arrest or apoptosis by inhibiting DNA replication. In the course of our search for bioactive metabolites from the marine sponges, Psammaplin A was found to have some anticancer properties, the possible mechanism of which was studied. Methods: Cell viability was determined by Cell Counting Kit-8 (CCK-8) to count living RAW264.7 cells by combining 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-8) and 1-methoxy-phenazine methosulfate (1-methoxy-PMS). The effect of Psammaplin A on DNA replication was carried out in SV40 DNA replication system in vitro. The activities of topoisomerase I and polymerase alpha-primase were measured by the relaxation of superhelical plasmid DNA and the incorporation of [3H]dTTP to the template respectively. The ssDNA binding activity of RPA was assessed by Gel Mobility Shift Assay (GMSA). Results: We have found that Psammaplin A delivers significant cytotoxic activity against the RAW264.7 cell line. It was also found that Psammaplin A could substantially inhibit SV40 DNA replication in vitro, in which polymerase alpha-primase is one of its main targets. Conclusion: Taken together, we suggest that psammaplin A-induced cytotoxicity may correlate with its inhibition on DNA replication. Psammaplin A has the potential to be developed as an anticancer drug.
Camptothecin-psammaplin A hybrids as topoisomerase I and HDAC dual-action inhibitors
Eur J Med Chem 2018 Jan 1;143:2005-2014.PMID:29150335DOI:10.1016/j.ejmech.2017.11.021.
Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of camptothecin derivatives and HDAC inhibitors. To exploit this synergy in a single active compound, we designed new dual-acting multivalent molecules simultaneously targeting topoisomerase I and HDAC. In particular, a selected compound containing a camptothecin and the Psammaplin A scaffold showed a broad spectrum of antiproliferative activity, with IC50 values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted in CD-1 nude mice and very high tolerability.
Psammaplin A, a chitinase inhibitor isolated from the Fijian marine sponge Aplysinella rhax
Bioorg Med Chem 2002 Apr;10(4):1123-8.PMID:11836123DOI:10.1016/s0968-0896(01)00372-8.
Several brominated tyrosine derived compounds, psammaplins A (1), K (2) and L (3) as well as bisaprasin (4) were isolated from the Fijian marine sponge Aplysinella rhax during a bioassay guided isolation protocol. Their structures were determined using NMR and MS techniques. Psammaplin A was found to moderately inhibit chitinase B from Serratia marcescens, the mode of inhibition being non-competitive. Crystallographic studies suggest that a disordered Psammaplin A molecule is bound near the active site. Interestingly, Psammaplin A was found to be a potent antifungal agent.