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

Molecular Formula	C11H15N5O3S
Molecular Weight	297.334
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/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
Antimicrobial and antiviral activity of xylosyl-methylthio-adenosine, a naturally occurring analogue of methylthio-adenosine from Doris verrucosa.	1991 Dec 1	1765135
Design and evaluation of 5'-modified nucleoside analogs as prodrugs for an E. coli purine nucleoside phosphorylase mutant.	2005	16247956
Homozygous deletions of methylthioadenosine phosphorylase in human biliary tract cancers.	2005 Dec	16373701
Implications of P16/CDKN2A deletion in pleural mesotheliomas.	2005 Jul	15950811
Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications.	2005 Nov	16224217
Natural history of S-adenosylmethionine-binding proteins.	2005 Oct 14	16225687
Comparative analysis of RNA regulatory elements of amino acid metabolism genes in Actinobacteria.	2005 Oct 3	16202131
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
Tissue microarray analysis of methylthioadenosine phosphorylase protein expression in melanocytic skin tumors.	2006 Apr	16618867
Methylthioadenosine phosphorylase gene deletions are frequently detected by fluorescence in situ hybridization in conventional chondrosarcomas.	2006 Apr 15	16631464
Development of high-throughput spermidine synthase activity assay using homogeneous time-resolved fluorescence.	2006 Apr 15	16472757
Methylthioadenosine and polyamine biosynthesis in a Saccharomyces cerevisiae meu1delta mutant.	2006 Apr 28	16530730
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
Circadian pharmacology of L-alanosine (SDX-102) in mice.	2006 Feb	16505107
EFA (9-beta-D-erythrofuranosyladenine) is an effective salvage agent for methylthioadenosine phosphorylase-selective therapy of T-cell acute lymphoblastic leukemia with L-alanosine.	2006 Feb 1	16234352
Promoter-hypermethylation is causing functional relevant downregulation of methylthioadenosine phosphorylase (MTAP) expression in hepatocellular carcinoma.	2006 Jan	16081515
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
Differential regulation of the JNK/AP-1 pathway by S-adenosylmethionine and methylthioadenosine in primary rat hepatocytes versus HuH7 hepatoma cells.	2006 Jun	16469827
Lack of methylthioadenosine phosphorylase expression in mantle cell lymphoma is associated with shorter survival: implications for a potential targeted therapy.	2006 Jun 15	16778103
Histone H3 lysine 4 dimethylation signals the transcriptional competence of the adiponectin promoter in preadipocytes.	2006 Jun 23	16613853
S-adenosylmethionine or 5'-methylthioadenosine are unable to prevent fumonisin B1 hepatotoxicity in mice despite increased oxidation in liver.	2006 Nov-Dec	17080400
The effect of a novel transition state inhibitor of methylthioadenosine phosphorylase on pemetrexed activity.	2006 Oct	17041099
Methylthioadenosine reverses brain autoimmune disease.	2006 Sep	16786535
Toxoplasma gondii purine nucleoside phosphorylase biochemical characterization, inhibitor profiles, and comparison with the Plasmodium falciparum ortholog.	2006 Sep 1	16829527
The methionine salvage pathway compound 4-methylthio-2-oxobutanate causes apoptosis independent of down-regulation of ornithine decarboxylase.	2006 Sep 28	16870157
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
Inhibition of human betaine-homocysteine methyltransferase expression by S-adenosylmethionine and methylthioadenosine.	2007 Jan 1	16953798
[Regulation of methionine/cysteine biosynthesis in Corynebacterium glutamicum and related genomes].	2007 Jan-Feb	17380901
Role of methionine adenosyltransferase 2A and S-adenosylmethionine in mitogen-induced growth of human colon cancer cells.	2007 Jul	17631143
Update on chondrosarcomas.	2007 Jul	17545802
Methylthioadenosine phosphorylase (MTAP) in hearing: gene disruption by chromosomal rearrangement in a hearing impaired individual and model organism analysis.	2007 Jul 15	17534888
A potential predictive marker for response to interferon in malignant melanoma.	2007 Jun	17537037
Role of S-adenosyl-L-methionine in liver health and injury.	2007 May	17464973
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 20:40:29 UTC 2023` Edited by `admin` on `Fri Dec 15 20:40:29 UTC 2023`
Record UNII	634Z2VK3UQ
Record Status	`Validated (UNII)`
Record Version

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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