Compounds > bisdethiobis(methylthio)gliotoxin
Page last updated: 2024-12-08

bisdethiobis(methylthio)gliotoxin

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Description

bisdethiobis(methylthio)gliotoxin: structure given in first source; a platelet activating factor antagonist [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID194564
CHEMBL ID1088981
SCHEMBL ID18652994
MeSH IDM0139881

Synonyms (30)

Synonym
(3r,5as,6s,10ar)-6-hydroxy-3-(hydroxymethyl)-2-methyl-3,10a-bis(methylsulfanyl)-6,10-dihydro-5ah-pyrazino[1,2-a]indole-1,4-dione
s,s-dimethyl gliotoxin
bisdethiobis(methylthio)gliotoxin
dimethylgliotoxin
74149-38-5
bis(methylthio)gliotoxin
bdbm50315535
3r,10ar-dithiomethyl gliotoxin a
CHEMBL1088981 ,
AC1L4YI4 ,
pyrazino(1,2-a)indole-1,4-dione, 2,3,5a,6,10,10a-hexahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-3,10a-bis(methylthio)-, (3r-(3alpha,5abeta,6beta,10aalpha))-
fr-49175
fr 49175
gtpl3150
(3r,5as,6s,10ar)-6-hydroxy-3-(hydroxymethyl)-2-methyl-3,10a-bis(methylsulfanyl)-1h,2h,3h,4h,5ah,6h,10h,10ah-piperazino[1,2-a]indole-1,4-dione
bis(methylsulfanyl)gliotoxin
bmgt
bis(methylthio)gliotoxin (fr-49175)
SCHEMBL18652994
NCGC00380667-01
mfcd00133146
bis(methylthio)gliotoxin, 99%
CS-0203642
(3r,5as,6s,10ar)-6-hydroxy-3-(hydroxymethyl)-2-methyl-3,10a-bis(methylthio)-2,3,5a,6,10,10a-hexahydropyrazino[1,2-a]indole-1,4-dione
DTXSID70995590
6-hydroxy-3-(hydroxymethyl)-2-methyl-3,10a-bis(methylsulfanyl)-2,3,5a,6,10,10a-hexahydropyrazino[1,2-a]indole-1,4-dione
Q27077740
bis(methylthio)gliotoxin (fr-49175) is known as a paf receptor ligand.
HY-N9710
AKOS040761419

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)		0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Pathways (1)

PathwayProteinsCompounds
gliotoxin inactivation17

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Farnesyl pyrophosphate synthaseHomo sapiens (human)IC50 (µMol)100.00000.00020.71099.3600AID475974
Cysteine protease Trypanosoma brucei rhodesienseIC50 (µMol)50.00000.00313.87667.7500AID475976
Histone-lysine N-methyltransferase EHMT2Homo sapiens (human)IC50 (µMol)100.00000.00251.14809.2000AID646185
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (24)

Processvia Protein(s)Taxonomy
cholesterol biosynthetic processFarnesyl pyrophosphate synthaseHomo sapiens (human)
geranyl diphosphate biosynthetic processFarnesyl pyrophosphate synthaseHomo sapiens (human)
farnesyl diphosphate biosynthetic processFarnesyl pyrophosphate synthaseHomo sapiens (human)
negative regulation of transcription by RNA polymerase IIHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
cellular response to starvationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
regulation of DNA replicationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
DNA methylation-dependent heterochromatin formationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
synaptonemal complex assemblyHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
spermatid developmentHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
long-term memoryHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
fertilizationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
peptidyl-lysine dimethylationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
regulation of protein modification processHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
organ growthHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
phenotypic switchingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
negative regulation of gene expression via chromosomal CpG island methylationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
response to ethanolHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
behavioral response to cocaineHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
oocyte developmentHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
neuron fate specificationHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
response to fungicideHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
cellular response to cocaineHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
cellular response to xenobiotic stimulusHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
negative regulation of autophagosome assemblyHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
negative regulation of transcription by RNA polymerase IIHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (17)

Processvia Protein(s)Taxonomy
RNA bindingFarnesyl pyrophosphate synthaseHomo sapiens (human)
protein bindingFarnesyl pyrophosphate synthaseHomo sapiens (human)
metal ion bindingFarnesyl pyrophosphate synthaseHomo sapiens (human)
dimethylallyltranstransferase activityFarnesyl pyrophosphate synthaseHomo sapiens (human)
geranyltranstransferase activityFarnesyl pyrophosphate synthaseHomo sapiens (human)
RNA polymerase II transcription regulatory region sequence-specific DNA bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
transcription corepressor bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
p53 bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
protein bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
zinc ion bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
protein-lysine N-methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
enzyme bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
histone H3K9 methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
histone H3K27 methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
C2H2 zinc finger domain bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
histone H3K56 methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
histone H3K9me2 methyltransferase activityHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
promoter-specific chromatin bindingHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (6)

Processvia Protein(s)Taxonomy
nucleoplasmFarnesyl pyrophosphate synthaseHomo sapiens (human)
cytosolFarnesyl pyrophosphate synthaseHomo sapiens (human)
cytoplasmFarnesyl pyrophosphate synthaseHomo sapiens (human)
nucleusHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
nucleoplasmHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
nuclear speckHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
chromatinHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
nucleusHistone-lysine N-methyltransferase EHMT2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (22)

Assay IDTitleYearJournalArticle
AID475976Inhibition of Trypanosoma brucei brucei recombinant rhodesain after 5 mins by spectrofluorimetry2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID476017Toxicity in ip dosed ddY mouse2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID646185Inhibition of HMT-G9a using S-adenosylmethionine and biotinylated H3 peptide after 1 hr2012Journal of natural products, Jan-27, Volume: 75, Issue:1
Gliotoxin analogues from a marine-derived fungus, Penicillium sp., and their cytotoxic and histone methyltransferase inhibitory activities.
AID475975Antitrypanosomal activity against Trypanosoma brucei brucei 427-221a after 40 hrs by bioluminescence assay2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID475986Cytotoxicity against HUVEC2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID475974Inhibition of farnesyl protein transferase2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID476020Immunomodulatory activity in macrophage assessed as inhibition of phagocytosis2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID646184Cytotoxicity against mouse P388 cells after 96 hrs by MTT assay2012Journal of natural products, Jan-27, Volume: 75, Issue:1
Gliotoxin analogues from a marine-derived fungus, Penicillium sp., and their cytotoxic and histone methyltransferase inhibitory activities.
AID646186Inhibition of HMT-set7/9 using S-adenosylmethionine and biotinylated H3 peptide at 100 uM after 1 hr2012Journal of natural products, Jan-27, Volume: 75, Issue:1
Gliotoxin analogues from a marine-derived fungus, Penicillium sp., and their cytotoxic and histone methyltransferase inhibitory activities.
AID623322Antiinvasive activity against human DU145 cells at 15 to 60 uM after 24 hrs by cell invasion assay2011Journal of natural products, Oct-28, Volume: 74, Issue:10
Glionitrin B, a cancer invasion inhibitory diketopiperazine produced by microbial coculture.
AID475977Inhibition of Trypanosoma brucei brucei recombinant cathepsin B assessed after 5 mins by spectrofluorimetry2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID623318Inhibition of human DU145 cells invasion at 60 uM after 24 hrs by cell invasion assay2011Journal of natural products, Oct-28, Volume: 74, Issue:10
Glionitrin B, a cancer invasion inhibitory diketopiperazine produced by microbial coculture.
AID475978Cytotoxicity against human Jurkat cells after 40 hrs bioluminescence assay2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID475994Inhibition of PAF2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID475981Selectivity index, ratio of IC50 for human Jurkat cells to IC50 for Trypanosoma brucei brucei2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID623315Cytotoxicity against human DU145 cells at 2.5 to 80 uM after 24 hrs by cell counting kit analysis2011Journal of natural products, Oct-28, Volume: 74, Issue:10
Glionitrin B, a cancer invasion inhibitory diketopiperazine produced by microbial coculture.
AID475985Cytotoxicity against human HeLa cells2010Bioorganic & medicinal chemistry, Apr-01, Volume: 18, Issue:7
Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (13)

TimeframeStudies, This Drug (%)All Drugs %
pre-19903 (23.08)18.7374
1990's0 (0.00)18.2507
2000's1 (7.69)29.6817
2010's6 (46.15)24.3611
2020's3 (23.08)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 12.28

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index12.28 (24.57)
Research Supply Index2.64 (2.92)
Research Growth Index4.92 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (12.28)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (7.69%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other12 (92.31%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
pentamidine
Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of PNEUMOCYSTIS pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects.. pentamidine : A diether consisting of pentane-1,5-diol in which both hydroxyl hydrogens have been replaced by 4-amidinophenyl groups. A trypanocidal drug that is used for treatment of cutaneous leishmaniasis and Chagas disease.		2.0510aromatic ether;
carboxamidine;
diether		anti-inflammatory agent;
antifungal agent;
calmodulin antagonist;
chemokine receptor 5 antagonist;
EC 2.3.1.48 (histone acetyltransferase) inhibitor;
NMDA receptor antagonist;
S100 calcium-binding protein B inhibitor;
trypanocidal drug;
xenobiotic
galactose
galactopyranose : The pyranose form of galactose.		2.2110D-galactose;
galactopyranose		Escherichia coli metabolite;
mouse metabolite
gliotoxin
Gliotoxin: A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent.. gliotoxin : A pyrazinoindole with a disulfide bridge spanning a dioxo-substituted pyrazine ring; mycotoxin produced by several species of fungi.		10.74100dipeptide;
organic disulfide;
organic heterotetracyclic compound;
pyrazinoindole		antifungal agent;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor;
immunosuppressive agent;
mycotoxin;
proteasome inhibitor
melarsoprol
Melarsoprol: Arsenical used in trypanosomiases. It may cause fatal encephalopathy and other undesirable side effects.		2.0510triazines
paclitaxel
Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).		2.0610taxane diterpenoid;
tetracyclic diterpenoid		antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
1-hexadecyl-2-acetyl-glycero-3-phosphocholine
Platelet Activating Factor: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.. 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine : A 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine betaine which has hexadecyl as the alkyl group. PAF is a potent phospholipid activator and mediator of many leukocyte functions, including platelet aggregation, inflammation, and anaphylaxis.		3.99402-acetyl-1-alkyl-sn-glycero-3-phosphocholineantihypertensive agent;
beta-adrenergic antagonist;
bronchoconstrictor agent;
hematologic agent;
vasodilator agent
ws 7739 b
FR 900452: platelet activating factor antagonist from fermentatiion products of Streptomyces phaeofaciens; MF C22-H25-N3-O3-S		3.0710
galactomannan
galactomannan: a galectin inhibitor. galactomannan : A heteroglycan consisting of a mannan backbone with galactose side groups.		2.2110oligosaccharide
ascofuranone
ascofuranone: structure. ascofuranone : A dihydroxybenzaldehyde that is 2,4-dihydroxybenzaldehyde which is substituted by a (2E,6E)-7-[(2S)-5,5-dimethyl-4-oxotetrahydrofuran-2-yl]-3-methylocta-2,6-dien-1-yl group at position 3, chlorine at position 5, and a methyl group at position 6. A meroterpenoid produced by the soil fungus, Acremonium sclerotigenum. It is a promising drug candidate against the tropical disease, African trypanosomiasis.		2.0510dihydroxybenzaldehyde;
meroterpenoid;
monochlorobenzenes;
olefinic compound;
resorcinols;
sesquiterpenoid;
tetrahydrofuranone		angiogenesis inhibitor;
antilipemic drug;
antineoplastic agent;
antiprotozoal drug;
fungal metabolite
spirotryprostatin a
spirotryprostatin A: structure in first source		2.0510
6-methoxyspirotryprostatin b
6-methoxyspirotryprostatin B: cytotoxic compound from the marine-derived fungus Aspergillus sydowi; structure in first source. 6-methoxyspirotryprostatin B : An indole alkaloid isolated from a marine-derived fungal strain Aspergillus sydowii PFW1-13 and has been shown to exhibit cytotoxic activity.		2.0510aromatic ether;
azaspiro compound;
indole alkaloid;
indolones		antineoplastic agent;
Aspergillus metabolite
mannans
[no description available]		2.2110
ginkgolide b
[no description available]		2.0210
ConditionIndicatedRelationship StrengthStudiesTrials
Cancer of Prostate
[description not available]		02.0610
Prostatic Neoplasms
Tumors or cancer of the PROSTATE.		02.0610
Leukemia P388
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.		02.0710
Congenital Zika Syndrome
[description not available]		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.2510
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510
Aspergillus Infection
[description not available]		03.4720
Aspergillosis
Infections with fungi of the genus ASPERGILLUS.		03.4720
Sensitivity and Specificity
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)		02.9910
Anaphylactic Reaction
[description not available]		01.9610
Anaphylaxis
An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.		01.9610
Allergic Reaction
[description not available]		02.8810
Endotoxin Shock
[description not available]		02.8810
Hypersensitivity
Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.		02.8810
Nephrosis
Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.		02.8810
Shock, Septic
Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.		02.8810
Allergic Bronchopulmonary Mycosis
[description not available]		02.2110