6-Thioguanine

6-Thioguanine is an anti-leukemia and immunosuppressant agent, acts as an inhibitor of SARS and MERS coronavirus papain-like proteases (PLpros) and also potently inhibits USP2 activity, with IC50s of 25 μM and 40 μM for Plpros and recombinant human USP2, respectively.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> Deubiquitinase

Signaling Pathways >> Anti-infection >> SARS-CoV

Research Areas >> Inflammation/Immunology

Research Areas >> Cancer

Research Areas >> Infection

IC50: 25 μM (PLpros), 40 μM (Recombinant human USP2)[3]

6-Thioguanine is an anti-leukemia and immunosuppressant agent, acts as an inhibitor of SARS and MERS coronavirus papain-like proteases (PLpros) and also potently inhibits USP2 activity, with IC50s of 25 μM and 40 μM for Plpros and recombinant human USP2, respectively[1]. 6-Thioguanine affects the methylation of cytosine residues by purified DNA methyltransferases including human DNMT1 and bacterial HpaII methylase. 6-Thioguanine (1 or 3 μM) decreases global cytosine methylation in Jurkat T cells and cytosine methylation in human cells at 3 μM[2]. 6-Thioguanine (18.75, 37.50, or 75.00 μM) adversely affects cell viability, but with no effect on LDH or ALT activity[3].

Treatments consists of 3 thiopurines (azathioprine, 6-mercaptopurine, and 6-thioguanine) at each of 6 concentrations (0.468, 0.937, 1.875, 3.750, 7.500, and 15.000 μM). Each thiopurinee is dissolved in DMSO solution to achieve a concentration of 10 mg/mL. Sterile filtered maintenance medium is used to further dilute each thiopurine solution to each of the 6 treatment concentrations. Twenty-four hours after the hepatocytes are plated on 96-well culture[3].

[1]. Chuang SJ, et al. 6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2. Sci Rep. 2018 Feb 15;8(1):3102.

[2]. Wang H, et al. 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. 2009 Mar 17;48(10):2290-9.

[3]. LaDuke KE, et al. Effects of azathioprine, 6-mercaptopurine, and 6-thioguanine on canine primary hepatocytes. Am J Vet Res. 2015 Jul;76(7):649-55.

BAY 11-7082 | P5091 | PR-619 | VLX1570 | Degrasyn(WP1130) | P 22077 | DUBs-IN-2 | ML364 | NSC 687852 | GNE-6776 | ML 323 | HBX 19818 | IU1 | LDN-57444

MOLECULAR FORMULA :

C5-H5-N5-S

MOLECULAR WEIGHT :

167.21

WISWESSER LINE NOTATION :

T56 BNM FYM INJ FUS HZ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Human

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Gastrointestinal - other changes Blood - hemorrhage Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

54 mg/kg

TOXIC EFFECTS :

Gastrointestinal - other changes Blood - hemorrhage Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LD10 - Lethal Dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1600 mg/kg

TOXIC EFFECTS :

Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

23720 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - conjunctive irritation Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

55990 ug/kg/5D-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

56 mg/kg/2W-I

TOXIC EFFECTS :

Blood - normocytic anemia Blood - changes in leukocyte (WBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

650 mg/kg/26W-I

TOXIC EFFECTS :

Blood - changes in erythrocyte (RBC) count Blood - changes in leukocyte (WBC) count Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

46500 ug/kg/5D-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

19950 ug/kg/4D-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

23700 ug/kg/13D-I

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from large intestine Nutritional and Gross Metabolic - body temperature increase Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

5700 ug/kg/13D-I

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from large intestine Nutritional and Gross Metabolic - body temperature increase Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

25 mg/kg

SEX/DURATION :

female 12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

10 mg/kg

SEX/DURATION :

female 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Sister chromatid exchange

TEST SYSTEM :

Rodent - hamster Lung

DOSE/DURATION :

15 ug/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 139,149,1984 *** REVIEWS *** TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5676 No. of Facilities: 18 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 82 (estimated) No. of Female Employees: 27 (estimated)