Cyclopiazonic acid (T3D3736)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2010-05-05 19:41:24 UTC
Update Date2014-12-24 20:26:28 UTC
Accession NumberT3D3736
Identification
Common NameCyclopiazonic acid
ClassSmall Molecule
DescriptionCyclopiazonic acid (CPA) is a myxotoxin originally isolated from Penicillium cyclopium and subsequently from Penicillium griseofulvum, Penicillium camembertii, Aspergillus flavus and Aspergillus versicolor. It is often found co-occurring with aflatoxins. CPA is a natural contaminant of corn, peanuts, and sunflowers, as well as various types of cheese, sausages, and salamis. It may also occur in eggs, milk and meats from animal that have consumed CPA-contaminated feed and is toxic in high concentrations. (7, 2)
Compound Type
  • Amide
  • Amine
  • Food Toxin
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
.alpha.-Cyclopiazonic acid
10-Acetyl-11-hydroxy-7,7-dimethyl-2,6,6a,7,11a,11b-hexahydro-9H-pyrrolo[1',2':2,3]isoindolo[4,5,6-cd]indol-9-one
alpha-Cyclopiazonate
alpha-Cyclopiazonic acid
CPA
Cyclopiazonate
Chemical FormulaC20H20N2O3
Average Molecular Mass336.384 g/mol
Monoisotopic Mass336.147 g/mol
CAS Registry Number18172-33-3
IUPAC Name5-acetyl-6-hydroxy-8,8-dimethyl-7,16-diazapentacyclo[9.6.1.0²,⁹.0³,⁷.0¹⁵,¹⁸]octadeca-1(17),5,11(18),12,14-pentaen-4-one
Traditional Name5-acetyl-6-hydroxy-8,8-dimethyl-7,16-diazapentacyclo[9.6.1.0²,⁹.0³,⁷.0¹⁵,¹⁸]octadeca-1(17),5,11(18),12,14-pentaen-4-one
SMILESCC(=O)C1=C(O)N2C(C3C(CC4=C5C(NC=C35)=CC=C4)C2(C)C)C1=O
InChI IdentifierInChI=1S/C20H20N2O3/c1-9(23)14-18(24)17-16-11-8-21-13-6-4-5-10(15(11)13)7-12(16)20(2,3)22(17)19(14)25/h4-6,8,12,16-17,21,25H,7H2,1-3H3
InChI KeyInChIKey=RLOAZVAJNNPPDI-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 3-alkylindoles. 3-alkylindoles are compounds containing an indole moiety that carries an alkyl chain at the 3-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassIndoles
Direct Parent3-alkylindoles
Alternative Parents
Substituents
  • 3-alkylindole
  • Isoindole or derivatives
  • Isoindoline
  • Pyrrolizine
  • Benzenoid
  • Heteroaromatic compound
  • Vinylogous amide
  • Vinylogous acid
  • Pyrroline
  • Pyrrolidine
  • Pyrrole
  • Ketone
  • Ketene acetal or derivatives
  • Azacycle
  • Alkanolamine
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.17 g/LALOGPS
logP2.47ALOGPS
logP3.08ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)3.56ChemAxon
pKa (Strongest Basic)2ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area73.4 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity104 m³·mol⁻¹ChemAxon
Polarizability36.22 ųChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0049000000-beed7ad8d422dddd235e2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fri-0139000000-74b4d3a12818ba276b0f2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-0930000000-0c3b3885c6f053326fc92016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000l-0069000000-f82fe95bc7b5e0693f152016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-1091000000-c68a07a4a2e1691b83c82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0600-9180000000-429a3089cb5b2f2add852016-08-03View Spectrum
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (6)
Mechanism of ToxicityCyclopiazonic acid is potent and specific inhibitor of the endoplasmic and sarcoplasmic reticulum Ca+-dependent ATPases, which are essential for calcium reuptake in the muscle contraction-relaxation cycle. CPA blocks the calcium access channel and rigidifies a subset of transmembrane helices in a nonnative configuration that is incompatible with calcium binding. Inhibition of Ca2+-ATPases results in cell death through the activation of stress-response and apoptotic pathways within the endoplasmic reticulum and mitochondria. CPA can also induce both secretion and mRNA levels of proinflammatory cytokines, likely leading to macrophage activation and immunotoxic effects. In addition, it has been shown to be mutagenic and genotoxic. Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity. (1, 2, 4, 5)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseLD50: 13 mg/kg (Intraperitoneal, Mouse) (3) LD50: 2.3 mg/kg (Intraperitoneal, Rat) (4)
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesCyclopiazonic acid (CPA) is a myxotoxin originally isolated from Penicillium cyclopium and subsequently from Penicillium griseofulvum, Penicillium camembertii, Aspergillus flavus and Aspergillus versicolor. It is often found co-occurring with aflatoxins. CPA is a natural contaminant of corn, peanuts, and sunflowers, as well as various types of cheese, sausages, and salamis. It may also occur in eggs, milk and meats from animal that have consumed CPA-contaminated feed. (7, 2)
Minimum Risk LevelNot Available
Health EffectsCyclopiazonic acid affects muscle function and may also be immunotoxic, genotoxic, and mutagenic. (2, 3, 4)
SymptomsAnimals studies have shown cyclopiazonic acid to cause symptoms such as tremors, convulsions, dyspnoea, hypokinesia, hypothermia, sedation, tachycardia, and tachypnoea. (3)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID2908
ChEMBL IDNot Available
ChemSpider ID2805
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCyclopiazonic_acid
References
Synthesis ReferenceNot Available
MSDST3D3736.pdf
General References
  1. Moncoq K, Trieber CA, Young HS: The molecular basis for cyclopiazonic acid inhibition of the sarcoplasmic reticulum calcium pump. J Biol Chem. 2007 Mar 30;282(13):9748-57. Epub 2007 Jan 26. [17259168 ]
  2. Marin ML, Wong SS, Pestka JJ: Increased IL-1, IL-6 and TNF alpha secretion and mRNA levels in WEHI-3 cells exposed to cyclopiazonic acid. Toxicology. 1996 Nov 15;114(1):67-79. [8931762 ]
  3. Nishie K, Cole RJ, Dorner JW: Toxicity and neuropharmacology of cyclopiazonic acid. Food Chem Toxicol. 1985 Sep;23(9):831-9. [4043883 ]
  4. Sorenson WG, Tucker JD, Simpson JP: Mutagenicity of tetramic mycotoxin cyclopiazonic acid. Appl Environ Microbiol. 1984 Jun;47(6):1355-7. [6430233 ]
  5. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
  6. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  7. Wikipedia. Cyclopiazonic acid. Last Updated 13 February 2010. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
General Function:
Protein homodimerization activity
Specific Function:
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A1
Uniprot ID:
O14983
Molecular Weight:
110251.36 Da
References
  1. Moncoq K, Trieber CA, Young HS: The molecular basis for cyclopiazonic acid inhibition of the sarcoplasmic reticulum calcium pump. J Biol Chem. 2007 Mar 30;282(13):9748-57. Epub 2007 Jan 26. [17259168 ]
Target Details
2. Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
General Function:
S100 protein binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle.
Gene Name:
ATP2A2
Uniprot ID:
P16615
Molecular Weight:
114755.765 Da
References
  1. Moncoq K, Trieber CA, Young HS: The molecular basis for cyclopiazonic acid inhibition of the sarcoplasmic reticulum calcium pump. J Biol Chem. 2007 Mar 30;282(13):9748-57. Epub 2007 Jan 26. [17259168 ]
Target Details
3. Sarcoplasmic/endoplasmic reticulum calcium ATPase 3
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A3
Uniprot ID:
Q93084
Molecular Weight:
113976.23 Da
References
  1. Moncoq K, Trieber CA, Young HS: The molecular basis for cyclopiazonic acid inhibition of the sarcoplasmic reticulum calcium pump. J Biol Chem. 2007 Mar 30;282(13):9748-57. Epub 2007 Jan 26. [17259168 ]
Target Details
4. Solute carrier family 22 member 1
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
Target Details
5. Solute carrier family 22 member 11
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular Weight:
59970.945 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
Target Details
6. Solute carrier family 22 member 2
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
Target Details
7. Solute carrier family 22 member 6
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
Target Details
8. Solute carrier family 22 member 7
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular Weight:
60025.025 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
Target Details
9. Solute carrier family 22 member 8
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]