Rubratoxin A
(Synonyms: 红色青霉毒素A) 目录号 : GC40285A selective PP2A inhibitor
Cas No.:22467-31-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Rubratoxin A is a natural mycotoxin and competitive inhibitor of protein phosphatase 2A (PP2A; IC50 = 170 nM). It has no significant effect on several other phosphatases, including PP1, PP2B, and protein tyrosine phosphatase 1B. Rubratoxin A drives overphosphorylation of PP2A substrate proteins in cultured cells treated for three hours at 20 µM. It causes suppression of tumor metastasis and reduction of primary tumor volume in mouse xenografts.
| Cas No. | 22467-31-8 | SDF | |
| 别名 | 红色青霉毒素A | ||
| Canonical SMILES | O=C1C2=C(C[C@@]([C@H](O)[C@]3([H])CC=CC(O3)=O)([H])CC(C(OC4=O)=O)=C4[C@H](O)[C@]2([H])[C@H](O)CCCCCC)C(O)O1 | ||
| 分子式 | C26H32O11 | 分子量 | 520.5 |
| 溶解度 | DMSO: soluble,Ethanol: soluble,Methanol: soluble | 储存条件 | Store at -20°C |
| 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 | 1.9212 mL | 9.6061 mL | 19.2123 mL |
| 5 mM | 0.3842 mL | 1.9212 mL | 3.8425 mL |
| 10 mM | 0.1921 mL | 0.9606 mL | 1.9212 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。
Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis
Cancer Sci 2010 Mar;101(3):743-50.PMID:20028386DOI:10.1111/j.1349-7006.2009.01438.x.
Although cytostatin analog protein phosphatase 2A (PP2A)-specific inhibitors are promising candidates of a new type of anticancer drug, their development has been hindered because of their liability. To find new classes of PP2A-specific inhibitors, we conducted a screening with microbial metabolites and found that Rubratoxin A, a classical mycotoxin, is a highly specific and potent inhibitor of the enzyme. While Rubratoxin A inhibits PP2A at Ki = 28.7 nm, it hardly inhibited any other phosphatases examined. Rubratoxin B, a close analog, also specifically but weakly inhibits PP2A at Ki = 3.1 microM. The inhibition of intracellular PP2A in cultured cells is obviously observed with 20 microM Rubratoxin A treatment for 3 h, inducing the overphosphorylation in PP2A substrate proteins. Although rubratoxins and cytostatin differ in the apparent structures, these compounds share similarities in the structures in detail and PP2A-binding manners. Rubratoxin A showed higher suppression of tumor metastasis and reduction of the primary tumor volume than cytostatin in mouse experiments. As a successor of cytostatin analogs, Rubratoxin A should be a good compound leading to the development of antitumor drugs targeting PP2A.
Inhibitory effects of Rubratoxin A, a potent inhibitor of protein phosphatase 2, on the Ca2+-dependent contraction of skinned carotid artery from guinea pig
J Smooth Muscle Res 2019;55(0):14-22.PMID:31006724DOI:10.1540/jsmr.55.14.
Rubratoxin A, a potent inhibitor of PP2A, is known to suppress smooth muscle contraction. The inhibitory role of PP2A in smooth muscle contraction is still unclear. In order to clarify the regulatory mechanisms of PP2A on vascular smooth muscle contractility, we examined the effects of Rubratoxin A on the Ca2+-induced contraction of β-escin skinned carotid artery preparations from guinea pigs. Rubratoxin A at 1 µM and 10 µM significantly inhibited skinned carotid artery contraction at any Ca2+ concentration. The data fitting to the Hill equation in [Ca2+]-contraction relationship indicated that Rubratoxin A decreased Fmax-Ca2+ and increased [Ca2+]50, indices of Ca2+ sensitivity for the force and myosin-actin interaction, respectively. These results suggest that PP2A inhibition causes downregulation of the myosin light chain phosphorylation and direct interference with myosin-actin interaction.
A Cascade of Redox Reactions Generates Complexity in the Biosynthesis of the Protein Phosphatase-2 Inhibitor Rubratoxin A
Angew Chem Int Ed Engl 2017 Apr 18;56(17):4782-4786.PMID:28370936DOI:10.1002/anie.201701547.
Redox modifications are key complexity-generating steps in the biosynthesis of natural products. The unique structure of Rubratoxin A (1), many of which arise through redox modifications, make it a nanomolar inhibitor of protein phosphatase 2A (PP2A). We identified the biosynthetic pathway of 1 and completely mapped the enzymatic sequence of redox reactions starting from the nonadride 5. Six redox enzymes are involved, including four α-ketoglutarate- and iron(II)-dependent dioxygenases that hydroxylate four sp3 carbons; one flavin-dependent dehydrogenase that is involved in formation of the unsaturated lactone; and the ferric-reductase-like enzyme RbtH, which regioselectively reduces one of the maleic anhydride moieties in rubratoxin B to the γ-hydroxybutenolide that is critical for PP2A inhibition. RbtH is proposed to perform sequential single-electron reductions of the maleic anhydride using electrons derived from NADH and transferred through a ferredoxin and ferredoxin reductase pair.
High-pressure liquid chromatography of the mycotoxins, rubratoxins A and B, and its application to the analysis of urine and plasma for rubratoxin B
J Chromatogr 1978 Jun 1;153(1):115-26.PMID:580783DOI:10.1016/s0021-9673(00)89862-3.
The rubratoxins are toxic metabolites produced by Penicillium rubrum and P. purpurogenum on food and feedstuffs. Rubratoxin B is hepatotoxic, mutagenic and teratogenic. Rubratoxins A and B were resolved as sharp peaks in the order A-B by reversed-phase high-pressure liquid chromatography on a small-particle (10 micrometer) column in 3 min by an acetonitrile-water-ethyl acetate elution solvent (11:9.9:3), with detection by ultraviolet absorbance at 254 nm. The relationship between peak height and quantity injected was linear over a range of 0.25-5 microgram for Rubratoxin A and 0.05-5 microgram for rubratoxin B. Retention time and peak height and peak area were highly reproducible for both toxins. Detection was very sensitive, allowing detection of 3-5 ng rubratoxin B, and 15-20 ng Rubratoxin A. Quantitative recovery of rubratoxin B from spiked urine samples was obtained over a range of 5-40 microgram/ml, with maximum recovery from urine samples adjusted to pH 2 before extraction. Good recovery of rubratoxin B was also obtained from spiked plasma samples subjected to treatment with 3 N hydrochloric acid followed by extraction with ethyl acetate.
Growth and synthesis of rubratoxin by Penicillium rubrum in a chemically defined medium fortified with organic acids and intermediates of the tricarboxylic acid cycle
Mycopathologia 1976 Oct 22;59(3):137-42.PMID:1036609DOI:10.1007/BF00627873.
A sterile glucose-mineral salts broth was fortified with equimolar concentrations (10--3 M) of various organic acids and intermediates in the tricarboxylic acid cycle. Appropriate media were neutralized with 2 N NaOH, inoculated with spore suspensions or mycelial pellets of Penicillium rubrum and incubated quiescently for 14 days or with shaking for 5 days. Rubratoxins were recovered from culture filtrates by ether extraction and resolved by thin-layer chromatography. Toxin formation in quiescent cultures was enhanced by malonate but was not markedly affected by ethyl malonate, shikimate, and acetate or by isocitrate or oxaloacetate added in the presence of malonate. Citrate, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, and malonate when present in the medium alone or in conjunction with malonate caused a 15 to 50% reduction in rubratoxin formation. Acetyl-CoA (10--5 M/flask) caused an 80% increase in toxin yield. Rubratoxin formation in shake cultures was not affected by succinate and malonate. All other combinations of intermediates and malonate caused a 10 to 50% reduction in toxin formation. At 10--3 M, citrate enhanced rubratoxin B formation and stimulated Rubratoxin A production by as much as 100%. Above 10--3 M, citrate inhibited toxin production. Incorporation of [2-14C]acetate into rubratoxin was enhanced by malonate, fumarate, and malonate. A combination of pyruvate and malonate produced a 40% increase in [2-14C]acetate incorporation into rubratoxin. The highest reduction of labeled acetate incorporation (36%) was caused by succinate or alpha-ketoglutarate combined with malonate.