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6-Thioguanine

CAS No.
154-42-7
Chemical Name:
6-Thioguanine
Synonyms
THIOGUANINE;tioguanine;6-tg;2-AMINO-6-PURINETHIOL;lanvis;6-MERCAPTOGUANINE;2-AMINO-6-MERCAPTOPURINE;2-Amino-3,7-dihydropurine-6-thione;2-Amino-3,7-dihydro-6H-purine-6-thione;6H-Purine-6-thione, 2-amino-1,9-dihydro-
CBNumber:
CB6361837
Molecular Formula:
C5H5N5S
Molecular Weight:
167.19
MDL Number:
MFCD00233553
MOL File:
154-42-7.mol
MSDS File:
SDS
Last updated:2023-09-22 14:52:15

6-Thioguanine Properties

Melting point ≥300 °C(lit.)
Density 1.483 (estimate)
refractive index 1.5605 (estimate)
storage temp. 2-8°C
solubility Practically insoluble in water and in ethanol (96%). It dissolves in dilute solutions of alkali hydroxides.
form lyophilized powder
pka pKa 8.22 (Uncertain)
Boiling point 555.4±42.0 °C(Predicted)
color Yellow to green
Water Solubility soluble
Merck 14,9337
BRN 157765
Stability Stable for 1 year from date of purchase as supplied. Solutions in DMF may be stored at -20°C for up to 1 month.
CAS DataBase Reference 154-42-7(CAS DataBase Reference)
NCI Dictionary of Cancer Terms Tabloid; thioguanine
FDA UNII WIX31ZPX66
NCI Drug Dictionary Tabloid
ATC code L01BB03
Proposition 65 List Thioguanine
EPA Substance Registry System Thioguanine (154-42-7)

Pharmacokinetic data

Protein binding Probably low
Excreted unchanged in urine 40%
Volume of distribution 0.148(L/kg)
Biological half-life 80 minutes / -

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS06
Signal word  Danger
Hazard statements  H301
Precautionary statements  P301+P310
Hazard Codes  T,Xi
Risk Statements  25-23/24/25
Safety Statements  28-36/37/39-45-28A
RIDADR  UN 2811 6.1/PG 3
WGK Germany  3
RTECS  UP0740000
13
Hazard Note  Irritant
HazardClass  6.1
PackingGroup  III
HS Code  29335990
Toxicity LD50 oral in mouse: 160mg/kg
NFPA 704
1
3 0

6-Thioguanine price More Price(60)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich PHR3250 Thioguanine pharmaceutical secondary standard, certified reference material 154-42-7 500MG $201 2024-03-01 Buy
Sigma-Aldrich BP878 Tioguanine British Pharmacopoeia (BP) Reference Standard 154-42-7 100MG $257 2024-03-01 Buy
Sigma-Aldrich A4660 6-Thioguanine Hybri-Max , 50 ×, γ-irradiated, lyophilized powder, BioXtra, suitable for hybridoma 154-42-7 2.5mg $26.7 2024-03-01 Buy
Sigma-Aldrich 1660000 Thioguanine United States Pharmacopeia (USP) Reference Standard 154-42-7 200mg $164.8 2024-03-01 Buy
TCI Chemical T0212 6-Thioguanine >95.0%(HPLC) 154-42-7 1g $94 2024-03-01 Buy
Product number Packaging Price Buy
PHR3250 500MG $201 Buy
BP878 100MG $257 Buy
A4660 2.5mg $26.7 Buy
1660000 200mg $164.8 Buy
T0212 1g $94 Buy

6-Thioguanine Chemical Properties,Uses,Production

Description

6-Thioguanine (NSC 752, Thioguanine, 2-Amino-6-purinethiol), is an antineoplastic metabolic antagonist that inhibits DNA synthesis by being metabolically converted to 6-thioGMP. This inhibits purine biosynthesis at multiple steps, and may be phosphorylated and incorporated into DNA. In humans, it causes bone marrow depression and gastrointestinal toxicity. Due to safety problems it is currently less used as an antineoplastic agent but has some use as therapy for ulcerative colitis.

Chemical Properties

Crystalline, lyophilized, sterile, endot. It is white or slightly yellow powder with umami taste, easily soluble in water, but insoluble in organic solvents such as ethanol and acetone.

Originator

Thioguanine,Burroughs-Wellcome,US,1966

Uses

6-Thioguanine acts as an antineoplastic and purine antimetabolite. It is also useful as an inhibition of stimulated expression of TNF-related apoptosis-inducing ligand (TRAIL) protein. It is involved in the treatment of acute leukemias and Psoriasis. Further, it is used for the treatment of ulcerative colitis and autoimmune diseases.

Indications

6-Thioguanine is a purine analogue structurally related to 6-mercaptopurine and azathioprine. Thioguanine interferes with several enzymes required for de novo purine synthesis, and its metabolites are incorporated into DNA and RNA, further impeding nucleic acid synthesis. The mechanism of action of thioguanine in psoriasis is not clearly understood; it has been hypothesized to affect the proliferation and trafficking of lymphocytes as well as the proliferation of keratinocytes.

Definition

ChEBI: 6-Thioguanine is a 2-aminopurine that is the 6-thiono derivative of 2-amino-1,9-dihydro-6H-purine.

Application

6-Thioguanine is a variant of guanine with hydrogen bonding at the N-7 of the purine ring. Its association with cytosine alters the dimension of the base stacking. 6-Thioguanine usage in treating inflammatory bowel disease (IBD) contributes to nodular regenerative hyperplasia (NRH) in the liver.
6-Thioguanine has been used:
to induce autophagy and apoptosis in colorectal cancer cell lines HCT116
as a selection marker in the mutation and survival assay in chinese hamster lung fibroblasts culture V79
as a selection marker in clonogenic Lung metastasis assay of 4T1-luc cells

Manufacturing Process

A mixture of 2.7 grams of finely divided guanine, 10 grams of pulverized phosphorus pentasulfide, 10 ml of pyridine and 100 ml of tetralin was heated at 200°C with mechanical stirring for 5 hours. After cooling, the mixture was filtered and the insoluble residue treated with 150 ml of water and 50 ml of concentrated ammonium hydroxide. The ammoniacal solution was filtered, heated to boiling and acidified with acetic acid. Upon cooling, 2-amino-6- mercaptopurine precipitated as a dark yellow powder, according to US Patent 2,697,709.

brand name

Tioguanine is INN and BAN.

Therapeutic Function

Cancer chemotherapy

General Description

6-thioguanine appears as odorless or almost odorless pale yellow crystalline powder. The drug is available in 40-mg tablets for oral use. It is used to treat acute nonlymphocytic leukemia.

Air & Water Reactions

6-Thioguanine may be sensitive to prolonged exposure to air. Insoluble in water.

Reactivity Profile

6-Thioguanine is incompatible with strong oxidizing agents.

Fire Hazard

Flash point data for 6-Thioguanine are not available; however, 6-Thioguanine is probably combustible.

Biochem/physiol Actions

Ribosylated and phosphorylated by the same pathway as natural purine bases; as the nucleotide, inhibits a variety of cellular processes involved in nucleic acid synthesis. Has a long history as an effective treatment of leukemia.

Mechanism of action

The mechanism of action involves incorporation of thetriphosphate into DNA and RNA, resulting in inhibition ofprocessing and function. Thioguanine is a purine antagonist. It is a pro-drug that is converted intracellullarly directly to thioguanine monophosphate (also called 6-thioguanylic acid) (TGMP) by the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT). TGMP is further converted to the di- and triphosphates, thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP). The cytotoxic effect of thioguanine is a result of the incorporation of these nucleotides into DNA. Thioguanine has some immunosuppressive activity.1 Thioguanine is specific for the S phase of the cell cycle.

Side effects

Dose-related myelosuppression is the major adverse effect produced by 6-thioguanine. Patients deficient in thiopurine methyltransferase (TPMT), a cytosolic enzyme required for metabolism of 6-thioguanine, are at heightened risk. Other adverse effects include gastrointestinal complaints and elevations of liver transaminases. There have been rare reports of more serious hepatotoxicity, including acute hepatitis, acute cholestasis, and hepatic venoocclusive disease.

Safety Profile

Poison by ingestion andintraperitoneal routes. Human mutation data reported. Anexperimental teratogen. Other reproductive effects. Ahuman skin irritant. When heated to decomposition itemits very toxic fumes of SOx and NOx.

Synthesis

Thioguanine, 2-aminopurin-6-thiol (30.1.2.12), is made from 2,8-dichloro- 6-hydroxypurine (30.1.2.7), in which the second chlorine atom at C2 is replaced with an amino group when reacted with ammonia, forming 2-amino-8-chloro-6-hydroxy-purine (30.1.2.7), which is then reduced by hydrogen iodide to 2-aminopurin-6-ol (30.1.2.11). Replacement of the hydroxyl group with a mercapto group at C6 is carried out by reacting it with phosphorous pentasulfide, which forms thioguanine (30.1.2.12).

Synthesis_154-42-7

Veterinary Drugs and Treatments

Thioguanine may be useful as adjunctive therapy for acute lymphocytic or granulocytic leukemia in dogs or cats.

Drug interactions

Potentially hazardous interactions with other drugs
Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis).

Metabolism

Tioguanine undergoes extensive metabolism in the liver and other tissues to several active and inactive metabolites. Tioguanine is inactivated mainly by methylation to aminomethylthiopurine; small amounts are deaminated to thioxanthine, and may go on to be oxidised by xanthine oxidase to thiouric acid, but inactivation is essentially independent of xanthine oxidase and is not affected by inhibition of the enzyme. 24-46
% of the dose is excreted in the urine within 24 hours. It is excreted in the urine almost entirely as metabolites

storage

Room temperature

Purification Methods

It crystallises from H2O as needles. It has UV at 258 and 347nm (H2O, pH 1) and 242, 270 and 322nm max (H2O, pH 11). [Elion & Hitchings J Am Chem Soc 77 1676 1955, Fox et al. J Am Chem Soc 80 1669 1958.] It is an antineoplastic agent [Kataoka et al. Cancer Res 44 519 1984]. [Beilstein 26 III/IV 3926.]

References

1) Wang and Wang (2009), 6-thioguanine perturbs cytosine methylation at the CpG dinucleotide site by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo; Biochemistry, 48 2290
2) Yuan et al. (2011), 6-thioguanine reactivates epigenetically silenced genes in acute lymphoblastic leukemia cells by facilitating proteasome-mediated degradation of DNMT1; Cancer Res., 71 1904
3) Bohon and de los Santos (2005), Effect of 6-thioguanine on the stability of duplex DNA; Nucleic Acid Res., 33 2880
4) Issaeva et al. (2010), 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance; Cancer Res., 70 6268

Global( 342)Suppliers
Supplier Tel Email Country ProdList Advantage
Hebei Yanxi Chemical Co., Ltd.
+8617531190177 peter@yan-xi.com China 5960 58
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View Lastest Price from 6-Thioguanine manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
6-Thioguanine pictures 2023-09-23 6-Thioguanine
154-42-7
US $70.00-10.00 / kg 1kg 0.99 10 tons Hebei Yanxi Chemical Co., Ltd.
6-Thioguanine pictures 2023-09-06 6-Thioguanine
154-42-7
US $0.00 / KG 1KG 99% 500000kg Hebei Guanlang Biotechnology Co., Ltd.
6-Thioguanine pictures 2023-07-26 6-Thioguanine
154-42-7
US $30.00 / kg 1kg 99% 1000tons Henan Bao Enluo International TradeCo.,LTD
  • 6-Thioguanine pictures
  • 6-Thioguanine
    154-42-7
  • US $70.00-10.00 / kg
  • 0.99
  • Hebei Yanxi Chemical Co., Ltd.
  • 6-Thioguanine pictures
  • 6-Thioguanine
    154-42-7
  • US $0.00 / KG
  • 99%
  • Hebei Guanlang Biotechnology Co., Ltd.
  • 6-Thioguanine pictures
  • 6-Thioguanine
    154-42-7
  • US $30.00 / kg
  • 99%
  • Henan Bao Enluo International TradeCo.,LTD
2-Amino-1,7(9)-dihydro-purine-6-thione 2-amino-6-mercaptopurine (50X)*gamma-irradiated C 2-amino-6-mercaptopurine crystalline 2-Amino-6-purinethiol (6-Thioguanine) 2-AMINO-6-MERCAPTOPURINE (50X)GAMMA-IRRA DIATED CEL Tioguanine(Thioguanine) 6-Thioguanine,~97% 6-THIOGUANIDE 2-AMINO-6-THIOLPURINE 2-amino-6-purinethio 6-THIOGUANINE 97% (HPLC) 2-Thioguanine Guanine, t purine antimetabolite: antimetabolite: inhibits nucleic acid replication 6H-Purine-6-thione, 2-amino-1,7-dihydro- 6-THIOGUANINE 2-amino-1,7-dihydro-6h-purin-6-thion 2-amino-1,7-dihydro-6h-purine-6-thion 2-aminopurine-6(1h)-thione 2-amino-purine-6(1h)-thion 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiol 5'-ribonucleotide dibutyryl cyclic AMP calcium salt complex coenzyme 2-Amino-9H-purine-6(1H)-thione 2-Amino-6-purinethiol ,98% 6-THIOGUANINE (6SG) 2-Amino-6-purinethiol,95% Thioguanine (200 mg) 6-TG/Thioguanine Thioguanine API 2-Amino-6-mercaptopurine 6-Mercaptoguanine 2-amino-1,9-dihydro-6H-purine-6-thione 2-Amino-1,7-dihydro-6H-purin-6-thion [Czech] 2-Amino-6-merkaptopurin [Czech] 2-Aminopurin-6-thiol [Czech] 2-amino-1,7-dihydro-6h-purine-6-thione 2-amino-6-merkaptopurin 2-amino-6-mp 2-aminopurin-6-thiol 2-aMino-1H-purine-6(7H)-thione 2-aMino-3H-purine-6(7H)-thione 2-amino-purine-6-thio 2-aminopurine-6-thiol 6-mercapto-2-aminopurine bw5071 nsc-752 purine-b-thiol,2-amino tabloid thio-guanin tioguanin wellcomeu3b 2-Amino-9H-purine-6-thiol 2-amino-6,7-dihydro-3H-purine-6-thione 6-Thioguanine> 6-Thioguanine (Solution) Mercaptopurine Impurity 6 6-Thioguanine USP/EP/BP