T3DB: Gliotoxin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (12)XML

Targets (12)

Record Information

Version

2.0

Creation Date

2009-11-13 22:01:12 UTC

Update Date

2014-12-24 20:26:12 UTC

Accession Number

T3D3604

Identification

Common Name

Gliotoxin

Class

Small Molecule

Description

Gliotoxin is a sulfur-containing antibiotic produced by several species of fungi, some of which are pathogens of humans such as Aspergillus, and also by species of Trichoderma, and Penicillium. Gliotoxin possesses immunosuppressive properties as it may suppress and cause apoptosis in certain types of cells of the immune system, including neutrophils, eosinophils, granulocytes, macrophages, and thymocytes. (5)

Compound Type

Amide
Amine
Fungal Toxin
Mycotoxin
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2,3,5a,6-Tetrahydro-6-hydroxy-3(hyroxymethyl)-2-methyl-10H-3a,10a-epidithio-pyrazinol[1,2alpha]indole-1,4-dione
6-Hydroxy-3-(hydroxymethyl)-2-methyl-2,3,6,10-tetrahydro-5aH-3,10a-epidithiopyrazino[1,2-a]indole-1,4-dione
7-hydroxy-11-hydroxymethyl-12-methyl-14,15-dithia-9,12-diazatetracyclo[9.2.2.01,9.03,8]pentadeca-3,5-diene-10,13-dione
Aspergillin
Gliotoxins
Glitoxin

Chemical Formula

C₁₃H₁₄N₂O₄S₂

Average Molecular Mass

326.391 g/mol

Monoisotopic Mass

326.039 g/mol

CAS Registry Number

67-99-2

IUPAC Name

7-hydroxy-11-(hydroxymethyl)-15-methyl-12,13-dithia-9,15-diazatetracyclo[9.2.2.0¹,⁹.0³,⁸]pentadeca-3,5-diene-10,14-dione

Traditional Name

gliotoxin

SMILES

CN1C(=O)C23CC4=CC=CC(O)C4N2C(=O)C1(CO)SS3

InChI Identifier

InChI=1S/C13H14N2O4S2/c1-14-10(18)12-5-7-3-2-4-8(17)9(7)15(12)11(19)13(14,6-16)21-20-12/h2-4,8-9,16-17H,5-6H2,1H3

InChI Key

InChIKey=FIVPIPIDMRVLAY-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as epipolythiodioxopiperazines. Epipolythiodioxopiperazines are compounds containing an epipolythiodioxopiperazine moiety, which consists of a 2,3-dithia-5,7-diazabicyclo[2.2.2]octane-6,8-dione ring system. One distinct characteristics of Epipolythiodioxopiperazines is the presence of unique di- or polysulfide bridges.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Diazinanes

Sub Class

Piperazines

Direct Parent

Epipolythiodioxopiperazines

Alternative Parents

Substituents

Alpha-amino acid or derivatives
Epipolythiodioxopiperazine
Indole or derivatives
N-alkylpiperazine
N-methylpiperazine
Dithiazinane
Tertiary carboxylic acid amide
Pyrrolidine
Carboxamide group
Lactam
Organic disulfide
Secondary alcohol
Carboxylic acid derivative
Azacycle
Organonitrogen compound
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Alcohol
Organic oxygen compound
Carbonyl group
Organic nitrogen compound
Organooxygen compound
Primary alcohol
Aliphatic heteropolycyclic compound

Molecular Framework

Aliphatic heteropolycyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

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 to light yellow solid.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	12.9 g/L	ALOGPS
logP	-0.36	ALOGPS
logP	-0.018	ChemAxon
logS	-1.4	ALOGPS
pKa (Strongest Acidic)	13.81	ChemAxon
pKa (Strongest Basic)	-3.2	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	81.08 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	81.69 m³·mol⁻¹	ChemAxon
Polarizability	30.61 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 GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-6891000000-dc755a3faf80227a1a30	2021-09-23	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-04	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-04	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, Positive	Not Available	2021-11-04	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-04	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-04	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	2021-11-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004j-0093000000-6c5b359bc2d3cc2081a5	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-0090000000-814b6894ed33c4bbd0a7	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-06ur-0091000000-7d83439eed6bfbd31908	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0009000000-85b64da2463f3f133a6a	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-0049000000-46f3823b9aa2e41be386	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-066r-3393000000-0294d462d54fd6f7cde7	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0009000000-95f8aa33f1fa88022b54	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4i-0029000000-11ac950ebb2f67150fd5	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0fr6-9120000000-203d8b9fa3d5f9a1520a	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004i-0009000000-98bf454948e4c3f35f0c	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-004i-0009000000-d85fccb9caf720b47b9b	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0udi-5091000000-cf96ab72715599cb355c	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum

Toxicity Profile

Route of Exposure

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

Mechanism of Toxicity

Gliotoxin possesses immunosuppressive properties as it may suppress and cause apoptosis in certain types of cells of the immune system, including neutrophils, eosinophils, granulocytes, macrophages, and thymocytes. It also acts as an inhibitor of farnesyl transferase. Gliotoxin noncompetitively inhibits the chymotrypsin-like activity of the 20S proteasome and displays anti-inflammatory activity. It acts by blocking thiol groups in the cell membranes. Gliotoxin is also cytotoxic and causes neurite degeneration. 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. (5, 1, 2)

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

Minimum Risk Level

Not Available

Health Effects

Gliotoxin has immunosuppressive effects. It is also cytotoxic and causes neurite degeneration. (5, 1)

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

6223

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

Gliotoxin

References

Synthesis Reference

Not Available

MSDS

T3D3604.pdf

General References

Axelsson V, Holback S, Sjogren M, Gustafsson H, Forsby A: Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells. Biochem Biophys Res Commun. 2006 Jul 7;345(3):1068-74. Epub 2006 May 11. [16712786 ]
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 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
FERMENTEK MSDS for Gliotoxin [Link]
Wikipedia. Gliotoxin. Last Updated 1 April 2010. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Targets

Target Details

1. Protein farnesyltransferase subunit beta

General Function:: Zinc ion binding
Specific Function:: Essential subunit of the farnesyltransferase complex. Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X.
Gene Name:: FNTB
Uniprot ID:: P49356
Molecular Weight:: 48773.2 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	1.1 uM	Not Available	BindingDB 50134315
IC50	80 uM	Not Available	BindingDB 50134315

References

Van der Pyl D, Inokoshi J, Shiomi K, Yang H, Takeshima H, Omura S: Inhibition of farnesyl-protein transferase by gliotoxin and acetylgliotoxin. J Antibiot (Tokyo). 1992 Nov;45(11):1802-5. [1281813 ]
Leonard DM: Ras farnesyltransferase: a new therapeutic target. J Med Chem. 1997 Sep 12;40(19):2971-90. [9301658 ]
Vigushin DM, Brooke G, Willows D, Coombes RC, Moody CJ: Pyrazino[1,2-a]indole-1,4-diones, simple analogues of gliotoxin, as selective inhibitors of geranylgeranyltransferase I. Bioorg Med Chem Lett. 2003 Nov 3;13(21):3661-3. [14552752 ]

Target Details

2. Histone-lysine N-methyltransferase EHMT2

General Function:: Zinc ion binding
Specific Function:: Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.
Gene Name:: EHMT2
Uniprot ID:: Q96KQ7
Molecular Weight:: 132369.205 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.53 uM	Not Available	BindingDB 50134315
IC50	6.4 uM	Not Available	BindingDB 50134315

References

Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Sun Y, Takada K, Takemoto Y, Yoshida M, Nogi Y, Okada S, Matsunaga S: Gliotoxin analogues from a marine-derived fungus, Penicillium sp., and their cytotoxic and histone methyltransferase inhibitory activities. J Nat Prod. 2012 Jan 27;75(1):111-4. doi: 10.1021/np200740e. Epub 2011 Dec 12. [22148349 ]

Target Details

3. Geranylgeranyl transferase type-1 subunit beta

General Function:: Zinc ion binding
Specific Function:: Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Known substrates include RAC1, RAC2, RAP1A and RAP1B.
Gene Name:: PGGT1B
Uniprot ID:: P53609
Molecular Weight:: 42367.81 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	17 uM	Not Available	BindingDB 50134315

References

Vigushin DM, Brooke G, Willows D, Coombes RC, Moody CJ: Pyrazino[1,2-a]indole-1,4-diones, simple analogues of gliotoxin, as selective inhibitors of geranylgeranyltransferase I. Bioorg Med Chem Lett. 2003 Nov 3;13(21):3661-3. [14552752 ]

Target Details

4. Histone-lysine N-methyltransferase SUV39H1

General Function:: Zinc ion binding
Specific Function:: Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. Also weakly methylates histone H1 (in vitro). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.
Gene Name:: SUV39H1
Uniprot ID:: O43463
Molecular Weight:: 47907.065 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.26 uM	Not Available	BindingDB 50134315

References

Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]

Target Details

5. Nuclear factor NF-kappa-B p100 subunit

General Function:: Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.
Gene Name:: NFKB2
Uniprot ID:: Q00653
Molecular Weight:: 96748.355 Da

References

Pahl HL, Krauss B, Schulze-Osthoff K, Decker T, Traenckner EB, Vogt M, Myers C, Parks T, Warring P, Muhlbacher A, Czernilofsky AP, Baeuerle PA: The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB. J Exp Med. 1996 Apr 1;183(4):1829-40. [8666939 ]

Target Details

6. Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha

General Function:: Rab geranylgeranyltransferase activity
Specific Function:: Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1 prenylation and activation.
Gene Name:: FNTA
Uniprot ID:: P49354
Molecular Weight:: 44408.32 Da

References

Van der Pyl D, Inokoshi J, Shiomi K, Yang H, Takeshima H, Omura S: Inhibition of farnesyl-protein transferase by gliotoxin and acetylgliotoxin. J Antibiot (Tokyo). 1992 Nov;45(11):1802-5. [1281813 ]

Target Details

7. 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

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 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

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 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

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

10. 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

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

11. 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

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

12. 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

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 ]

Gliotoxin (T3D3604)

Structure for T3D3604: Gliotoxin

Targets

Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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