6-thio-dG (β-TGdR; 6-Thio-2'-Deoxyguanosine; BetaTGdR) is a nucleoside analog and a potent telomerase-mediated telomere disrupting compound with potential antitumor activity. It has anti-cancer properties. The observed IC50 values of cancer cells ranged from 0.7-2.9 μM, indicating high sensitivity to 6-thio-dG. 6-In telomerase-positive human cancer cells and hTERT-expressing human fibroblasts, Thio-dG causes telomere dysfunction and progressive telomere shortening. 6-thio-dG has been found to inhibit cell viability in tested cancer cells, with IC50 values ranging from 0.7 to 2.9 μM.

Physicochemical Properties

Molecular Formula	C10H13N5O3S
Molecular Weight	283.31
Exact Mass	283.073
Elemental Analysis	C, 42.40; H, 4.63; N, 24.72; O, 16.94; S, 11.32
CAS #	789-61-7
Related CAS #	789-61-7
PubChem CID	3000603
Appearance	White to yellow solid powder
Density	2.0±0.1 g/cm3
Boiling Point	709.1±70.0 °C at 760 mmHg
Flash Point	382.6±35.7 °C
Vapour Pressure	0.0±2.4 mmHg at 25°C
Index of Refraction	1.930
LogP	-0.91
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	19
Complexity	420
Defined Atom Stereocenter Count	3
SMILES	S=C1N=C(N)NC2N([C@H]3C[C@H](O)[C@@H](CO)O3)C=NC1=2
InChi Key	SCVJRXQHFJXZFZ-KVQBGUIXSA-N
InChi Code	InChI=1S/C10H13N5O3S/c11-10-13-8-7(9(19)14-10)12-3-15(8)6-1-4(17)5(2-16)18-6/h3-6,16-17H,1-2H2,(H3,11,13,14,19)/t4-,5+,6+/m0/s1
Chemical Name	2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H-purine-6-thione
Synonyms	6-Thio-2''-deoxyguanosine; Beta-TGdR; 6-thio-dG; 6thiodG; 6 thio dG; BetaTGdR; Beta TGdR
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	DNA/RNA Synthesis
ln Vitro	6-Thio-dG causes telomere dysfunction, which in turn causes telomere shortening in human fibroblasts and telomerase-positive human cancer cells. 6-thio-dG has been found to inhibit cell viability in tested cancer cells, with IC50 values ranging from 0.7 to 2.9 μM.[1]
ln Vivo	6-Thio-dG (2 mg/kg, i.p.) reduces the tumorigenicity of A549 Cells by causing telomere dysfunction in mice with A549 lung cancer xenografts.[1]
Cell Assay	In 96-well plates, cells are plated in growth media. After a week of incubation, the cells are treated every three days with DMSO or different concentrations of 6-thio-dG and 6-thioguanine. To determine the IC50 values for the CellTiterGlo luminescent cell viability assay, the 96-well plates are analyzed in accordance with the manufacturer's instructions. The drug concentration at which 50% of cells are inhibited by the drug is known as the IC50. To determine IC50 values, sigmoidal dose-response curves are utilized. The SDs are derived from two separate experiments, and each sample is examined in triplicate.
Animal Protocol	The mice used are 6 week old female athymic NCR nu/nu mice. Subcutaneous inoculation of 100 µL phosphate buffered saline (PBS) is used to inoculate the left and right dorsal flanks of the naked mice with A549 cells. Mice are randomly assigned to treatment groups for 6-thio-dG, 6-thioguanine, and control once tumors have grown to an average volume of 40 mm3. Three animals per group. Every two days for 17 days, animals receive intraperitoneal injections of a 100 µL DMSO/PBS mixture every mouse, at a dose of 2 mg/kg. Furthermore, for 16 days, a daily intratumoral injection of 2.5 mg/kg of athymic NCR nu/nu female mice in 50 µL of DMSO/PBS mixture is administered to various animals. Every day or every two days, the size of the tumor is measured with calipers and recorded.
ADME/Pharmacokinetics	Metabolism / Metabolites THE PHARMACOKINETICS OF RADIOLABELED 6-THIOGUANINE (TG) WERE COMPARED WITH THAT OF BETA-2'-DEOXYTHIOGUANOSINE (BETA-TGDR) AFTER IV ADMIN. URINARY EXCRETION OF THE RADIOLABEL WAS 75% OF THE DOSE 24 HR AFTER ADMIN. BOTH THIOPURINES WERE RAPIDLY & EXTENSIVELY DEGRADED & EXCRETED AS 6-THIOXANTHINE, INORGANIC SULFATE, S-METHYL-6-THIOXANTHINE, & 6-THIOURIC ACID IN ADDITION TO OTHER PRODUCTS. SMALL AMOUNTS OF UNCHANGED DRUG WERE ALSO EXCRETED. STUDIES SUGGEST THAT BETA-TGDR IS A LATENT FORM OF TG. SINCE RESISTANCE TO ANTILEUKEMIC AGENT 6-THIOGUANINE INEVITABLY DEVELOPS IN ANIMAL TUMORS, THIS NEW AGENT BETA-TGDR IS OF POTENTIAL CLINICAL USE.
References	[1]. Induction of telomere dysfunction mediated by the telomerase substrate precursor 6-thio-2'-deoxyguanosine. Cancer Discov. 2015 Jan;5(1):82-95.
Additional Infomation	Beta-Thioguanine Deoxyriboside is a thiopurine nucleoside derivative with antineoplastic activity. After conversion to the triphosphate, beta-thioguanine deoxyriboside is incorporated into DNA, resulting in inhibition of DNA replication. This agent is cytotoxic against leukemia cell lines and has demonstrated some activity against leukemia cells in vivo. Beta-thioguanine deoxyriboside demonstrates antineoplastic activity against 6-thioguanine-resistant tumor cells. (NCI04) See also: 6-Thioguanosine (annotation moved to). Therapeutic Uses STUDIES SUGGEST THAT BETA-TGDR IS A LATENT FORM OF TG. SINCE RESISTANCE TO ANTILEUKEMIC AGENT 6-THIOGUANINE INEVITABLY DEVELOPS IN ANIMAL TUMORS, THIS NEW AGENT BETA-TGDR IS OF POTENTIAL CLINICAL USE.

Solubility Data

Solubility (In Vitro)

DMSO: 50~56 mg/mL (176.5~197.7 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.83 mg/mL (2.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (2.93 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.83 mg/mL (2.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.5297 mL	17.6485 mL	35.2970 mL
	5 mM	0.7059 mL	3.5297 mL	7.0594 mL
	10 mM	0.3530 mL	1.7649 mL	3.5297 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.