Rubratoxin A
(right click,save link as to download,it is a temp file,please download as soon as possible, you can also use CTRL+S to save the whole html page)
Basic Info
| Common Name | Rubratoxin A(F04978) |
| 2D Structure | |
| Description | Rubratoxin A is a mycotoxin produced by fungi such as Penicillum rubrum and Penicillum purpurogenum, which are common soil fungi that sometimes contaminate animal feeds. Rubratoxins have been shown to be hepatotoxic, nephrotoxic, and splenotoxic. Studies on Rubratoxin A however have also indicated it may also have valuable antitumor and antimetastatic effects. (A2985, A2988) |
| FRCD ID | F04978 |
| CAS Number | 22467-31-8 |
| PubChem CID | 31181 |
| Formula | C26H32O11 |
| IUPAC Name | None |
| InChI Key | XOEFANNJIKAWGX-UHFFFAOYSA-N |
| InChI | InChI=1S/C26H32O11/c1-2-3-4-5-7-15(27)20-18-13(23(31)36-25(18)33)10-12(21(29)16-8-6-9-17(28)35-16)11-14-19(22(20)30)26(34)37-24(14)32/h6,9,12,15-16,20-23,27,29-31H,2-5,7-8,10-11H2,1H3 |
| Canonical SMILES | CCCCCCC(C1C(C2=C(CC(CC3=C1C(=O)OC3O)C(C4CC=CC(=O)O4)O)C(=O)OC2=O)O)O |
| Isomeric SMILES | CCCCCCC(C1C(C2=C(CC(CC3=C1C(=O)OC3O)C(C4CC=CC(=O)O4)O)C(=O)OC2=O)O)O |
| Synonyms |
10-((3,6-Dihydro-6-oxo-2H-pyran-2-yl)hydroxymethyl)-4,5,8,9,10,11-hexahydro-4,8-dihydroxy-5-(1-hydroxyheptyl)-1H-cyclonona(1,2-c:5,6-c')difuran-1,3,6-trione
RUBRATOXIN A
HSDB 3532
BRN 1633008
22467-31-8
AC1L1L2Y
1H-Cyclonona(1,2-c:5,6-c')difuran-1,3,6-trione, 10-((3,6-dihydro-6-oxo-2H-pyran-2-yl)hydroxymethyl)-4,5,8,9,10,11-hexahydro-4,8-dihydroxy-5-(1-hydroxyheptyl)-
1H-Cyclonona(c)furan-6,7-dicarboxylic anhydride, 9-((3,6-dihydro-6-oxo-2H-pyran-2-yl)hydroxymethyl)-3,4,5,8,9,10-hexahydro-1,5-dihydroxy-4-(1-hydroxyheptyl)-3-oxo-
LS-57685
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic acids and derivatives |
| Class | Carboxylic acids and derivatives |
| Subclass | Tetracarboxylic acids and derivatives |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Tetracarboxylic acids and derivatives |
| Alternative Parents | |
| Molecular Framework | Aliphatic heteropolycyclic compounds |
| Substituents | Tetracarboxylic acid or derivatives - Fatty alcohol - Dihydropyranone - 2-furanone - Fatty acyl - Pyran - Carboxylic acid anhydride - Dihydrofuran - Alpha,beta-unsaturated carboxylic ester - Enoate ester - Carboxylic acid ester - Hemiacetal - Lactone - Secondary alcohol - Organoheterocyclic compound - Oxacycle - Hydrocarbon derivative - Alcohol - Organic oxide - Organic oxygen compound - Organooxygen compound - Carbonyl group - Aliphatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as tetracarboxylic acids and derivatives. These are carboxylic acids containing exactly four carboxyl groups. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 520.531 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 8 |
| Complexity | 1050 |
| Monoisotopic Mass | 520.194 |
| Exact Mass | 520.194 |
| XLogP | 1.4 |
| Formal Charge | 0 |
| Heavy Atom Count | 37 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 7 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.7141 |
| Human Intestinal Absorption | HIA+ | 0.9569 |
| Caco-2 Permeability | Caco2- | 0.7037 |
| P-glycoprotein Substrate | Substrate | 0.7623 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8445 |
| Non-inhibitor | 0.8900 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8680 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.8173 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8706 |
| CYP450 2D6 Substrate | Non-substrate | 0.8782 |
| CYP450 3A4 Substrate | Substrate | 0.5722 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8122 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8976 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9095 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8369 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.5415 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9099 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.8489 |
| Non-inhibitor | 0.8155 | |
| AMES Toxicity | Non AMES toxic | 0.6981 |
| Carcinogens | Non-carcinogens | 0.9773 |
| Fish Toxicity | High FHMT | 0.9792 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9955 |
| Honey Bee Toxicity | High HBT | 0.7698 |
| Biodegradation | Not ready biodegradable | 0.7342 |
| Acute Oral Toxicity | II | 0.7169 |
| Carcinogenicity (Three-class) | Non-required | 0.5227 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.6116 | LogS |
| Caco-2 Permeability | 0.1838 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.0818 | LD50, mol/kg |
| Fish Toxicity | 1.0767 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.6734 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| 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 | 580783 |
Targets
- General Function:
- Steroid hormone binding
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients.
- Gene Name:
- ATP1A2
- Uniprot ID:
- P50993
- Molecular Weight:
- 112264.385 Da
- Mechanism of Action:
- Rubratoxin A inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Steroid hormone binding
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
- Gene Name:
- ATP1A3
- Uniprot ID:
- P13637
- Molecular Weight:
- 111747.51 Da
- Mechanism of Action:
- Rubratoxin A inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Protein serine/threonine phosphatase activity
- Specific Function:
- The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.
- Gene Name:
- PPP2R1A
- Uniprot ID:
- P30153
- Molecular Weight:
- 65307.81 Da
- Mechanism of Action:
- Rubratoxin A is a potent inhibitor of protein phosphatase 2A, exerting antitumor and antimetastatic effects. Inhibition may cause the phosphorylation of CREB and subsequent activation of natural killer cells via the stimulation of interleukin-2 release from T cells, contributing to antimetastatic effects. Focal adhesion kinase phosphorylation and paxillin phosphorylation that interfere with cell adhesion could be another antimetastatic effect.
References
- Wada S, Usami I, Umezawa Y, Inoue H, Ohba S, Someno T, Kawada M, Ikeda D: Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis. Cancer Sci. 2010 Mar;101(3):743-50. doi: 10.1111/j.1349-7006.2009.01438.x. Epub 2009 Nov 14. [20028386 ]
- General Function:
- Protein phosphatase type 2a regulator activity
- Specific Function:
- The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit.
- Gene Name:
- PPP2R1B
- Uniprot ID:
- P30154
- Molecular Weight:
- 66212.77 Da
- Mechanism of Action:
- Rubratoxin A is a potent inhibitor of protein phosphatase 2A, exerting antitumor and antimetastatic effects. Inhibition may cause the phosphorylation of CREB and subsequent activation of natural killer cells via the stimulation of interleukin-2 release from T cells, contributing to antimetastatic effects. Focal adhesion kinase phosphorylation and paxillin phosphorylation that interfere with cell adhesion could be another antimetastatic effect.
References
- Wada S, Usami I, Umezawa Y, Inoue H, Ohba S, Someno T, Kawada M, Ikeda D: Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis. Cancer Sci. 2010 Mar;101(3):743-50. doi: 10.1111/j.1349-7006.2009.01438.x. Epub 2009 Nov 14. [20028386 ]
- General Function:
- Protein serine/threonine phosphatase activity
- Specific Function:
- PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase.
- Gene Name:
- PPP2CB
- Uniprot ID:
- P62714
- Molecular Weight:
- 35574.85 Da
- Mechanism of Action:
- Rubratoxin A is a potent inhibitor of protein phosphatase 2A, exerting antitumor and antimetastatic effects. Inhibition may cause the phosphorylation of CREB and subsequent activation of natural killer cells via the stimulation of interleukin-2 release from T cells, contributing to antimetastatic effects. Focal adhesion kinase phosphorylation and paxillin phosphorylation that interfere with cell adhesion could be another antimetastatic effect.
References
- Wada S, Usami I, Umezawa Y, Inoue H, Ohba S, Someno T, Kawada M, Ikeda D: Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis. Cancer Sci. 2010 Mar;101(3):743-50. doi: 10.1111/j.1349-7006.2009.01438.x. Epub 2009 Nov 14. [20028386 ]
- General Function:
- Steroid hormone binding
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
- Gene Name:
- ATP1A1
- Uniprot ID:
- P05023
- Molecular Weight:
- 112895.01 Da
- Mechanism of Action:
- Rubratoxin A inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Sodium:potassium-exchanging atpase activity
- Specific Function:
- This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.Involved in cell adhesion and establishing epithelial cell polarity.
- Gene Name:
- ATP1B1
- Uniprot ID:
- P05026
- Molecular Weight:
- 35061.07 Da
- Mechanism of Action:
- Rubratoxin A inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Sodium:potassium-exchanging atpase activity
- Specific Function:
- This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
- Gene Name:
- ATP1B2
- Uniprot ID:
- P14415
- Molecular Weight:
- 33366.925 Da
- Mechanism of Action:
- Rubratoxin A inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Sodium:potassium-exchanging atpase activity
- Specific Function:
- This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.
- Gene Name:
- ATP1B3
- Uniprot ID:
- P54709
- Molecular Weight:
- 31512.34 Da
- Mechanism of Action:
- Rubratoxin A inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Transporter activity
- Specific Function:
- May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
- Gene Name:
- FXYD2
- Uniprot ID:
- P54710
- Molecular Weight:
- 7283.265 Da
- Mechanism of Action:
- Rubratoxin A inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.
- Specific Function:
- Gaba receptor binding
- Gene Name:
- PPP2CA
- Uniprot ID:
- P67775
- Molecular Weight:
- 35593.93 Da
- Mechanism of Action:
- Rubratoxin A is a potent inhibitor of protein phosphatase 2A, exerting antitumor and antimetastatic effects. Inhibition may cause the phosphorylation of CREB and subsequent activation of natural killer cells via the stimulation of interleukin-2 release from T cells, contributing to antimetastatic effects. Focal adhesion kinase phosphorylation and paxillin phosphorylation that interfere with cell adhesion could be another antimetastatic effect.
References
- Wada S, Usami I, Umezawa Y, Inoue H, Ohba S, Someno T, Kawada M, Ikeda D: Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis. Cancer Sci. 2010 Mar;101(3):743-50. doi: 10.1111/j.1349-7006.2009.01438.x. Epub 2009 Nov 14. [20028386 ]
- General Function:
- Sodium:potassium-exchanging atpase activity
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility.
- Gene Name:
- ATP1A4
- Uniprot ID:
- Q13733
- Molecular Weight:
- 114165.44 Da
- Mechanism of Action:
- Rubratoxin A inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]