GLIOTOXIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H14N2O4S2
Molecular Weight	326.391
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)[C@]23CC4=CC=C[C@H](O)[C@H]4N2C(=O)[C@@]1(CO)SS3

InChI

InChIKey=FIVPIPIDMRVLAY-RBJBARPLSA-N

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/t8-,9-,12+,13+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C13H14N2O4S2
Molecular Weight	326.391
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11522753 | https://www.ncbi.nlm.nih.gov/pubmed/26445050 | https://www.ncbi.nlm.nih.gov/pubmed/28736522 | https://www.ncbi.nlm.nih.gov/pubmed/15034210 | DOI: 10.1021/ja01250a051

Gliotoxin is a potent crystalline antibiotic substance produced during the growth of the imperfect fungus Gliocladium jimbriatum. It is a natural mycotoxin with immunosuppressive and antimicrobial activity. Gliotoxin acts as NOTCH2 transactivation inhibitor in human neoplasias. It induced growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with pronounced antitumor activity and favorable toxicity profile against breast cancer in vitro and in vivo.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Apoptosis 156 Target ID: map04210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11522753	Activator 1447
Protein farnesyltransferase 13 Target ID: CHEMBL2094108 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15034210	Inhibitor 8504	80.0 µM [IC50]
Geranylgeranyl transferase type I 7 Target ID: CHEMBL2095164 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15034210	Inhibitor 8504	17.0 µM [IC50]
Wnt signaling pathway 13 Target ID: map04310 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26445050	Inhibitor 8504
NOTCH2 transactivation 1 Target ID: NOTCH2 transactivation Sources: https://www.ncbi.nlm.nih.gov/pubmed/28736522	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Liver fibrosis 9 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11522753	Primary	Preclinical	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15034210	Primary	Preclinical	Unknown Approved Use Unknown
Colorectal cancer 102 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26445050	Primary	Basic research	Unknown Approved Use Unknown
Melanoma 88 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28736522	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
PKCdelta-mediated regulation of FLIP expression in human colon cancer cells.	2006-01-15	16052516
The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis.	2005-10	16151628
LaeA, a regulator of morphogenetic fungal virulence factors.	2005-09	16151250
Thiopental-induced apoptosis in lymphocytes is independent of CD95 activation.	2005-09	16129983
Cyclooxygenase-2 inhibitors decrease vascular endothelial growth factor expression in colon cancer cells by enhanced degradation of Sp1 and Sp4 proteins.	2005-08	15883203
Bioinformatic and expression analysis of the putative gliotoxin biosynthetic gene cluster of Aspergillus fumigatus.	2005-07-15	15979823
Enhanced human beta-defensin-2 (hBD-2) expression by corticosteroids is independent of NF-kappaB in colonic epithelial cells (CaCo2).	2005-07	16047468
Dehydroxymethylepoxyquinomicin, a novel nuclear factor-kappaB inhibitor, induces apoptosis in multiple myeloma cells in an IkappaBalpha-independent manner.	2005-07	16020669
Gliotoxin-induced cytotoxicity in three salmonid cell lines: cell death by apoptosis and necrosis.	2005-06	16046190
The mycotoxins citrinin and gliotoxin differentially affect production of the pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin-6, and the anti-inflammatory cytokine interleukin-10.	2005-06	15969670
Aspergillus mycotoxins and their effect on the host.	2005-05	16110799
Anandamide induces necrosis in primary hepatic stellate cells.	2005-05	15841466
The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis.	2005-04	15817772
Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes.	2005-03-15	15546954
Genes and molecules involved in Aspergillus fumigatus virulence.	2005-03	15813678
The ABC transporter gene in the sirodesmin biosynthetic gene cluster of Leptosphaeria maculans is not essential for sirodesmin production but facilitates self-protection.	2005-03	15707846
NF-kappaB inhibition accelerates apoptosis of bovine neutrophils.	2005-02-22	15720975
Fungal populations and mycotoxins in silage in Assiut and Sohag governorates in Egypt, with a special reference to characteristic Aspergilli toxins.	2005-02	15770455
TNF-alpha expression is transcriptionally regulated by RANK ligand.	2005-02	15389596
Production of gliotoxin on natural substrates by Trichoderma virens.	2005	15678558
Anti-apoptotic actions of the platelet-activating factor acetylhydrolase I alpha2 catalytic subunit.	2004-12-10	15456758
Gliotoxins disrupt alanine metabolism and glutathione production in C6 glioma cells: a 13C NMR spectroscopic study.	2004-12	15380625
Directed biosynthesis of fluorinated pseurotin A, synerazol and gliotoxin.	2004-11	15712670
Effects of infliximab on apoptosis and reverse signaling of monocytes from healthy individuals and patients with Crohn's disease.	2004-11	15626899
[Chemistry and biological effects of gliotoxin].	2004-11	15584558
Reversible disruption of tight junction complexes in the rat blood-brain barrier, following transitory focal astrocyte loss.	2004-10	15326610
Gliotoxin induces Mg2+ efflux from intact brain mitochondria.	2004-10	15234120
Effect and stability of gliotoxin, an Aspergillus fumigatus toxin, on in vitro rumen fermentation.	2004-09	15666981
The sirodesmin biosynthetic gene cluster of the plant pathogenic fungus Leptosphaeria maculans.	2004-09	15387811
Comparing a ciliate and a fish cell line for their sensitivity to several classes of toxicants by the novel application of multiwell filter plates to Tetrahymena.	2004-08-11	15636753
Amphotericin B enhances the synthesis and release of the immunosuppressive agent gliotoxin from the pulmonary pathogen Aspergillus fumigatus.	2004-08	15272057
Metallothionein prevents neurodegeneration and central nervous system cell death after treatment with gliotoxin 6-aminonicotinamide.	2004-07-01	15197737
Correlation between gliotoxin production and virulence of Aspergillus fumigatus in Galleria mellonella.	2004-07	15487324
Cytotoxic substances from Aspergillus fumigatus in oxygenated or poorly oxygenated environment.	2004-07	15487313
Allergen activates peripheral blood eosinophil nuclear factor-kappaB to generate granulocyte macrophage-colony stimulating factor, tumour necrosis factor-alpha and interleukin-8.	2004-07	15248852
Mechanism of action of the antifibrogenic compound gliotoxin in rat liver cells.	2004-07	15239107
Anti-apoptotic effect of nerve growth factor is lost in congenital insensitivity to pain with anhidrosis (CIPA) B lymphocytes.	2004-05	15114061
Effect of aeration on gliotoxin production by Aspergillus fumigatus in its culture filtrate.	2004-04	15180150
Cytotoxicity of fungal metabolites to lepidopteran (Spodoptera frugiperda) cell line (SF-9).	2004-02	15050836
Detection of Aspergillus fumigatus mycotoxins: immunogen synthesis and immunoassay development.	2004-02	14744451
Measurement of NAD(P)H oxidase-derived superoxide with the luminol analogue L-012.	2004-01-01	14732294
Effect of aeration on gliotoxin production by Aspergillus fumigatus in its culture filtrate.	2004-01	15008341
Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo.	2004	15034210
Influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in Jurkat T cells and human peripheral blood cells: anti-inflammatory and cytotoxic effects.	2003-12-01	14609739
Evidence for radiosensitizing by gliotoxin in HL-60 cells: implications for a role of NF-kappaB independent mechanisms.	2003-11-27	14647473
Pyrazino[1,2-a]indole-1,4-diones, simple analogues of gliotoxin, as selective inhibitors of geranylgeranyltransferase I.	2003-11-03	14552752
Concentration-dependent atypical intestinal absorption of cyclic phenylalanylserine: small intestine acts as an interface between the body and ingested compounds.	2003-11	14600416
Increasing local levels of neuregulin (glial growth factor-2) by direct infusion into areas of demyelination does not alter remyelination in the rat CNS.	2003-10	14622186
Accumulation of gliotoxin, a cytotoxic mycotoxin from Aspergillus fumigatus, in blue mussel (Mytilus edulis).	2003-09	14559081
Concentration-dependent preferences of absorptive and excretive transport cause atypical intestinal absorption of cyclic phenylalanylserine: small intestine acts as an interface between the body and ingested compounds.	2002	15244036

Patents

Sample Use Guides

In Vivo Use Guide

Rat: 3 mg/kg body wt

Route of Administration: Intraperitoneal

In Vitro Use Guide

Culture-activated (14-day) rat Hepatic stellate cells (HSCs) and Culture-activated (24-day) human (H2) HSCs cells were treated for 4 hours with 1.5 umol/L gliotoxin. Rat and human HSCs resulted in striking morphologic alterations within 1 hour as judged by light microscopy. HSCs changed from a flattened fibroblastic phenotype with distinct cell-cell interfaces to a substratum-detached, rounded, and blebbed morphology.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:14:13 GMT 2025` Edited by `admin` on `Mon Mar 31 22:14:13 GMT 2025`
Record UNII	5L648PH06K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GLIOTOXIN

Common Name

English

NSC-102866

Preferred Name

English

ASPERGILLIN

Common Name

English

S. N.-12870

Code

English

GLIOTOXIN [MI]

Common Name

English

10H-3,10A-EPIDITHIOPYRAZINO(1,2-A)INDOLE-1,4-DIONE, 2,3,5A,6-TETRAHYDRO-6-HYDROXY-3-(HYDROXYMETHYL)-2-METHYL-, (3R,5AS,6S,10AR)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C574