5'-METHYLTHIOADENOSINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H15N5O3S
Molecular Weight	297.334
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CSC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N2C=NC3=C2N=CN=C3N

InChI

InChIKey=WUUGFSXJNOTRMR-IOSLPCCCSA-N

InChI=1S/C11H15N5O3S/c1-20-2-5-7(17)8(18)11(19-5)16-4-15-6-9(12)13-3-14-10(6)16/h3-5,7-8,11,17-18H,2H2,1H3,(H2,12,13,14)/t5-,7-,8-,11-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15313459
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20529342

5-Methylthioadenosine (MTA) is a naturally occurring sulfur-containing nucleoside present in all mammalian tissues. The major source of MTA in cells is formed from S-adenosylmethionine during the synthesis of the polyamines spermine and spermidine. In most cells MTA does not accumulate is significant amounts and is rapidly metabolized by 5-methythioadenosine phosphorylase (MTAP) to yield adenine (Ade) and 5-methylthioribose-1-phosphate (MTR1P). The removal of accumulating MTA by MTAP is necessary for the cell to carry out polyamine metabolism, since MTA is a strong inhibitor of spermine synthase. Intracellular fluctuations in MTA levels could participate in the regulation of the liver proliferative response, and administration of MTA have hepatorptective effect in a model of CCl4-induced chronic liver damage.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
S-methyl-5-thioadenosine phosphorylase 1 Target ID: CHEMBL4941 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24148083	Substrate 661
Spermidine synthase 2 Target ID: CHEMBL4232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7241513	Inhibitor 8297
Spermine synthase 2 Target ID: CHEMBL4934 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7241513	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Melanoma 88 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20529342	Primary		Basic research	Unknown Approved Use Unknown
Liver injury 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11322199	Preventing		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Modeling and experiment yields the structure of acireductone dioxygenase from Klebsiella pneumoniae.	2002 Dec	12402029
Extracellular ATP is an autocrine/paracrine regulator of hypoxia-induced adventitial fibroblast growth. Signaling through extracellular signal-regulated kinase-1/2 and the Egr-1 transcription factor.	2002 Nov 22	12244041
Altered gene expression in liver from a murine model of hyperhomocysteinemia.	2003 Aug 22	12799373
Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites.	2003 Dec 12	14506228
Effect of clopidogrel administration to healthy volunteers on platelet phosphorylation events triggered by ADP.	2003 Feb	12588350
Characterisation of methionine adenosyltransferase from Mycobacterium smegmatis and M. tuberculosis.	2003 Jun 16	12809568
Pharmacology and mechanism of action of pemetrexed.	2004 Apr	15117425
Novel amino acid derived natural products from the ascidian Atriolum robustum: identification and pharmacological characterization of a unique adenosine derivative.	2004 Apr 22	15084123
Inhibition of lipopolysaccharide-stimulated TNF-alpha promoter activity by S-adenosylmethionine and 5'-methylthioadenosine.	2004 Aug	15064230
Crystal structure of yeast Ypr118w, a methylthioribose-1-phosphate isomerase related to regulatory eIF2B subunits.	2004 Aug 27	15215245
Methylthioadenosine phosphorylase from the archaeon Pyrococcus furiosus. Mechanism of the reaction and assignment of disulfide bonds.	2004 Dec	15606771
Picomolar transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase and X-ray structure with MT-immucillin-A.	2004 Jan 13	14705926
Delivery systems and molecular targets of mechanism-based therapies for GBM.	2004 Jul	15853584
Analogs of 1-phosphonooxy-2,2-dihydroxy-3-oxo-5-(methylthio)pentane, an acyclic intermediate in the methionine salvage pathway: a new preparation and characterization of activity with E1 enolase/phosphatase from Klebsiella oxytoca.	2004 Jul 15	15210152
Bacterial variations on the methionine salvage pathway.	2004 Mar 4	15102328
Antioxidant properties of S-adenosyl-L-methionine in Fe(2+)-initiated oxidations.	2004 May 15	15110395
Comprehensive analysis of the 9p21 region in neuroblastoma suggests a role for genes mapping to 9p21-23 in the biology of favourable stage 4 tumours.	2004 Sep 13	15305192
Methylthioadenosine phosphorylase gene is silenced by promoter hypermethylation in human lymphoma cell line DHL-9: another mechanism of enzyme deficiency.	2005 Apr	15753993
Homozygous deletions of methylthioadenosine phosphorylase in human biliary tract cancers.	2005 Dec	16373701
Bayesian phylogenetic analysis reveals two-domain topology of S-adenosylhomocysteine hydrolase protein sequences.	2005 Jan	15579379
Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse.	2005 Jan 20	15659501
Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion.	2005 Jul	15832197
The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code.	2005 Jul 1	15870070
Chemical mechanism and substrate specificity of RhlI, an acylhomoserine lactone synthase from Pseudomonas aeruginosa.	2005 Mar 1	15723540
A nucleosidase required for in vivo function of the S-adenosyl-L-methionine radical enzyme, biotin synthase.	2005 May	15911379
Natural history of S-adenosylmethionine-binding proteins.	2005 Oct 14	16225687
S-adenosylmethionine blocks collagen I production by preventing transforming growth factor-beta induction of the COL1A2 promoter.	2005 Sep 2	15983038
Fine-mapping loss of gene architecture at the CDKN2B (p15INK4b), CDKN2A (p14ARF, p16INK4a), and MTAP genes in head and neck squamous cell carcinoma.	2006 Apr	16618910
The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081.	2006 Dec 15	17173484
Comparative protein modeling of spermidine synthase from Plasmodium falciparum: A potential target for anti-malarial drug therapy.	2006 Dec 23	17597911
The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951.	2006 Jul	16818274
Lack of methylthioadenosine phosphorylase expression in mantle cell lymphoma is associated with shorter survival: implications for a potential targeted therapy.	2006 Jun 15	16778103
S-adenosylmethionine or 5'-methylthioadenosine are unable to prevent fumonisin B1 hepatotoxicity in mice despite increased oxidation in liver.	2006 Nov-Dec	17080400
Growth control of the eukaryote cell: a systems biology study in yeast.	2007	17439666
Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy.	2007 Apr 17	17439648
A novel approach for determining cancer genomic breakpoints in the presence of normal DNA.	2007 Apr 18	17440616
The complete genome sequence of Yersinia pseudotuberculosis IP31758, the causative agent of Far East scarlet-like fever.	2007 Aug	17784789
Enzymes as a special class of therapeutic target: clinical drugs and modes of action.	2007 Dec	17884461
The role of methionine recycling for ethylene synthesis in Arabidopsis.	2007 Jan	17144895
[Regulation of methionine/cysteine biosynthesis in Corynebacterium glutamicum and related genomes].	2007 Jan-Feb	17380901
Methylthioadenosine phosphorylase deficiency in Japanese osteosarcoma patients.	2007 Nov	17912432
Protein arginine methyltransferase 1: positively charged residues in substrate peptides distal to the site of methylation are important for substrate binding and catalysis.	2007 Nov 20	17960915
Metabolic signature of breast cancer cell line MCF-7: profiling of modified nucleosides via LC-IT MS coupling.	2007 Nov 29	18047657
Nicotinamide riboside kinase structures reveal new pathways to NAD+.	2007 Oct 2	17914902
Losses of 3p14 and 9p21 as shown by fluorescence in situ hybridization are early events in tumorigenesis of oral squamous cell carcinoma and already occur in simple keratosis.	2008 Apr	18163473
Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications.	2008 Apr 15	18237276
Leptin's mitogenic effect in human liver cancer cells requires induction of both methionine adenosyltransferase 2A and 2beta.	2008 Feb	18041713
S-adenosylmethionine and its products.	2008 Feb	17334902
Azetidine based transition state analogue inhibitors of N-ribosyl hydrolases and phosphorylases.	2008 Feb 28	18251493
S-adenosylmethionine inhibits lipopolysaccharide-induced gene expression via modulation of histone methylation.	2008 May	18393372

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Melanoma cell lines harboring wild type NRAS and BRAF (37-31E and MeWo), NRASQ61L mutation (SKMel 103 and SKMel 147) or BRAFV600E mutation (UACC903, Colo 829) were grown in complete medium and in the presence of increasing concentrations (from 1 uM till 600 uM) of methylthioadenosine (MTA). Wild type NRAS and BRAF melanoma cells (37-31E, MeWo), and melanoma cells harboring NRASQ61L (SKMel 147 and SKMel 103) showed a 50% inhibition of cell proliferation at 9.8 ± 0.4 μM, 18.9 ± 1.2 μM, 10.01 ± 0.2 μM and 21.2 ± 0.2 μM respectively, while the GI50 for BRAFV600E mutant cell lines was 6.1 ± 0.4 for UACC903 cells and 8.2 ± 0.3 for Colo 829 cells. BRAFV600E mutant cells showed a significant lower proliferation rate (p < 0.05) at 96 h using 10 μM MTA compared with wild type or NRASQ61L mutant cells. All melanoma cell lines were significantly (p < 0.01) more sensitive than normal MEFs (GI50>600 μM), reaching the maximum inhibition of proliferation between 10 μM and 600 μM concentration of MTA depending on the cell line.

Name

Type

Language

5'-METHYLTHIOADENOSINE

Systematic Name

English

5'-DEOXY-5'-METHYLTHIOADENOSINE

Systematic Name

English

7-(TETRAHYDRO-3,4-DIHYDROXY-5-(METHYLMERCAPTOMETHYL)-2-FURYL)ADENINE

Systematic Name

English

METHYLTHIOADENOSINE

Official Name

English

METHYLTHIOADENOSINE [INCI]

Common Name

English

5'-(METHYLTHIO)-5'-DEOXYADENOSINE

Systematic Name

English

5'-DEOXY(METHYLTHIO)ADENOSINE

Systematic Name

English

5'-(METHYLTHIO)ADENOSINE

Systematic Name

English

VITAMIN L(SUB 2)

Common Name

English

ADENOSINE, 5'-S-METHYL-5'-THIO-

Systematic Name

English

.BETA.-D-RIBOFURANOSE, 1-(6-AMINO-9H-PURIN-9-YL)-1-DEOXY-5-S-METHYL-5-THIO-

Common Name

English

VITAMIN L2

Common Name

English

5'-S-METHYLTHIOADENOSINE

Common Name

English

5'-DEOXY-5'-(METHYLTHIO)ADENOSINE

Systematic Name

English

5'-S-METHYL-5'-THIOADENOSINE

Systematic Name

English

NSC-335422

Code

English

Code System Code Type Description

DRUG BANK

DB02282