T3DB: Cytochalasin J

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (6)XML

Targets (6)

Record Information

Version

2.0

Creation Date

2010-04-16 22:10:27 UTC

Update Date

2014-12-24 20:26:21 UTC

Accession Number

T3D3681

Identification

Common Name

Cytochalasin J

Class

Small Molecule

Description

Cytochalasins are mycotoxins that have the ability to bind to actin filaments and block polymerization and the elongation of actin. As a result, they can change cellular morphology, inhibit cellular processes such as cell division, and cause cells to undergo apoptosis. Cytochalasins also have the ability to permeate cell membranes, prevent cellular translocation, cause cells to enucleate, and affect other aspects of biological processes unrelated to actin polymerization. Cytochalasin J is has been isolated from the fungus Phomopsis paspali. It also has shown CNS activity. (1, 2, 6, 7)

Compound Type

Amide
Amine
Fungal Toxin
Mycotoxin
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(3S,3aR,4S,6aR,7E,13E,15R)-3-Benzyl-6,12,15-trihydroxy-4,10,12-trimethyl-5-methylene-2,3,3a,4,5,6,6a,9,10,11,12,15-dodecahydro-1H-cycloundeca[d]isoindol-1-one
7,18,21-Trihydroxy-16,18-dimethyl-10-phenyl-(11)cytochalasa-6(12),13,19-trien-1-one
Kodocytochalasin 2
Paspalin P
Paspalin P II

Chemical Formula

C₂₈H₃₅NO₅

Average Molecular Mass

465.581 g/mol

Monoisotopic Mass

465.252 g/mol

CAS Registry Number

56144-22-0

IUPAC Name

3-benzyl-6,12,15-trihydroxy-4,10,12-trimethyl-5-methylidene-1H,2H,3H,4H,5H,6H,6aH,9H,10H,11H,12H,15H,15bH-cycloundeca[e]isoindole-1,11-dione

Traditional Name

3-benzyl-6,12,15-trihydroxy-4,10,12-trimethyl-5-methylidene-2H,3H,4H,6H,6aH,9H,10H,15H,15bH-cycloundeca[e]isoindole-1,11-dione

SMILES

CC1C2C(CC3=CC=CC=C3)NC(=O)C22C(\C=C\CC(C)C(=O)C(C)(O)\C=C\C2O)C(O)C1=C

InChI Identifier

InChI=1S/C28H35NO5/c1-16-9-8-12-20-24(31)18(3)17(2)23-21(15-19-10-6-5-7-11-19)29-26(33)28(20,23)22(30)13-14-27(4,34)25(16)32/h5-8,10-14,16-17,20-24,30-31,34H,3,9,15H2,1-2,4H3,(H,29,33)/b12-8+,14-13+

InChI Key

InChIKey=DMUBZPWTFAPROZ-KRQHZRJMSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as cytochalasans. These are fungal metabolites structurally characterized by the presence of an isoindolone nucleus fused to a macrocyclic ring, which can either a lactone, as in cytochalasin B, a carbonate, as in cytochalasin E, or a carbocycle, as in cytochalasin D, H, and K.

Kingdom

Organic compounds

Super Class

Alkaloids and derivatives

Class

Cytochalasans

Sub Class

Not Available

Direct Parent

Cytochalasans

Alternative Parents

Substituents

Carbocyclic cytochalasan skeleton
Cytochalasan
Isoindolone
Isoindoline
Isoindole
Isoindole or derivatives
Acyloin
Monocyclic benzene moiety
Benzenoid
2-pyrrolidone
Pyrrolidone
Cyclic alcohol
Tertiary alcohol
Pyrrolidine
Carboxamide group
Cyclic ketone
Secondary carboxylic acid amide
Ketone
Lactam
Secondary alcohol
Organoheterocyclic compound
Azacycle
Carboxylic acid derivative
Polyol
Alcohol
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Organic oxygen compound
Carbonyl group
Organonitrogen compound
Organooxygen compound
Organic nitrogen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	137-139°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.033 g/L	ALOGPS
logP	2.29	ALOGPS
logP	2.67	ChemAxon
logS	-4.2	ALOGPS
pKa (Strongest Acidic)	12.83	ChemAxon
pKa (Strongest Basic)	-0.33	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	106.86 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	132.37 m³·mol⁻¹	ChemAxon
Polarizability	50.62 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0000900000-6166edd911e8c979c438	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-001j-2004900000-62cb9f9ca17e29c2720a	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0zfu-9803000000-270a1dc60e3899a64971	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0000900000-93af0e3cf07ec39caa4f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01ot-0001900000-6a135cdbebc3b471eb93	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9024200000-2d614b46a29c3eda8c8b	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (3)

Mechanism of Toxicity

Cytochalasins are known to bind to the barbed, fast growing plus ends of microfilaments, which then blocks both the assembly and disassembly of individual actin monomers from the bound end. Once bound, cytochalasin essentially caps the end of the new actin filament. One cytochalasin will bind to one actin filament. By blocking the polymerization and elongation of actin, cytochalasins can change cellular morphology, inhibit cellular processes such as cell division, and cause cells to undergo apoptosis. (1, 2, 6)

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Cytochalasin J is has been isolated from the fungus Phomopsis paspali. (7)

Minimum Risk Level

Not Available

Health Effects

Major biological effects of cytochalasins include inhibition of the division of cytoplasm, reversible inhibition of cell movement, induction of nuclear extrusion, inhibition of such processes as phagocytosis, platelet aggregation and clot retraction, glucose transport, thyroid secretion, and release of growth hormone. Some cytochalasins have been shown to have developmental effects. (7)

Symptoms

Not Available

Treatment

Consider activated charcoal after gastrointestinal absportion. Nitroprusside is recommended to reverse peripheral ischemia secondary to vasoconstriction and for the treatment of hypertension. Anticoagulant therapy with intravenous heparin is also recommended. (4)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

Not Available

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

Not Available

General References

Haidle AM, Myers AG: An enantioselective, modular, and general route to the cytochalasins: synthesis of L-696,474 and cytochalasin B. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12048-53. Epub 2004 Jun 18. [15208404 ]
Cooper JA: Effects of cytochalasin and phalloidin on actin. J Cell Biol. 1987 Oct;105(4):1473-8. [3312229 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [15509185 ]
Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2010; CCIS Volume 143, edition expires Feb, 2010. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2010; CCIS Volume 143, edition expires Feb, 2010.
Cytochalasin. Wikipedia. Last Updated 12 April 2010. [Link]
Sigma Aldrich 1996. Technical Bulletin AL-126: The Cytochalasins. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Actin, alpha cardiac muscle 1

General Function:: Myosin binding
Specific Function:: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:: ACTC1
Uniprot ID:: P68032
Molecular Weight:: 42018.6 Da

References

Haidle AM, Myers AG: An enantioselective, modular, and general route to the cytochalasins: synthesis of L-696,474 and cytochalasin B. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12048-53. Epub 2004 Jun 18. [15208404 ]
Cytochalasin. Wikipedia. Last Updated 12 April 2010. [Link]

Target Details

2. Actin, alpha skeletal muscle

General Function:: Structural constituent of cytoskeleton
Specific Function:: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:: ACTA1
Uniprot ID:: P68133
Molecular Weight:: 42050.67 Da

References

Haidle AM, Myers AG: An enantioselective, modular, and general route to the cytochalasins: synthesis of L-696,474 and cytochalasin B. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12048-53. Epub 2004 Jun 18. [15208404 ]
Cytochalasin. Wikipedia. Last Updated 12 April 2010. [Link]

Target Details

3. Actin, aortic smooth muscle

General Function:: Protein kinase binding
Specific Function:: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:: ACTA2
Uniprot ID:: P62736
Molecular Weight:: 42008.57 Da

References

Haidle AM, Myers AG: An enantioselective, modular, and general route to the cytochalasins: synthesis of L-696,474 and cytochalasin B. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12048-53. Epub 2004 Jun 18. [15208404 ]
Cytochalasin. Wikipedia. Last Updated 12 April 2010. [Link]

Target Details

4. Actin, cytoplasmic 1

General Function:: Tat protein binding
Specific Function:: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:: ACTB
Uniprot ID:: P60709
Molecular Weight:: 41736.37 Da

References

Haidle AM, Myers AG: An enantioselective, modular, and general route to the cytochalasins: synthesis of L-696,474 and cytochalasin B. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12048-53. Epub 2004 Jun 18. [15208404 ]
Cytochalasin. Wikipedia. Last Updated 12 April 2010. [Link]

Target Details

5. Actin, cytoplasmic 2

General Function:: Ubiquitin protein ligase binding
Specific Function:: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:: ACTG1
Uniprot ID:: P63261
Molecular Weight:: 41792.48 Da

References

Haidle AM, Myers AG: An enantioselective, modular, and general route to the cytochalasins: synthesis of L-696,474 and cytochalasin B. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12048-53. Epub 2004 Jun 18. [15208404 ]
Cytochalasin. Wikipedia. Last Updated 12 April 2010. [Link]

Target Details

6. Actin, gamma-enteric smooth muscle

General Function:: Atp binding
Specific Function:: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:: ACTG2
Uniprot ID:: P63267
Molecular Weight:: 41876.495 Da

References

Haidle AM, Myers AG: An enantioselective, modular, and general route to the cytochalasins: synthesis of L-696,474 and cytochalasin B. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12048-53. Epub 2004 Jun 18. [15208404 ]
Cytochalasin. Wikipedia. Last Updated 12 April 2010. [Link]

Cytochalasin J (T3D3681)

Structure for T3D3681: Cytochalasin J

Targets

References

References

References

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