| Systematic (IUPAC) name | |
|---|---|
| 2-amino-7H-purine-6-thiol | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| MedlinePlus | a682099 |
| Pregnancy cat. | ? |
| Legal status | ? |
| Routes | oral |
| Pharmacokinetic data | |
| Bioavailability | 30% (range 14% to 46%) |
| Metabolism | Intracellular |
| Half-life | 80 minutes (range 25-240 minutes) |
| Identifiers | |
| CAS number | 154-42-7 |
| ATC code | L01BB03 |
| PubChem | CID 2723601 |
| DrugBank | APRD00290 |
| ChemSpider | 2005804 |
| UNII | WIX31ZPX66 |
| KEGG | D08603 |
| ChEMBL | CHEMBL727 |
| Chemical data | |
| Formula | C5H5N5S |
| Mol. mass | 167.193 g/mol |
| SMILES | eMolecules & PubChem |
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Tioguanine (INN), formerly thioguanine (BAN), is a drug that is used in the treatment of cancer.[1]
It belongs to the family of drugs called antimetabolites. It is a guanine analog.
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Its principal use is in acute leukaemias and chronic myeloid leukaemia.
It has been investigated for use in treatment of psoriasis.[2]
As a guanine analogue, it is transformed inside the cell into 6-thioguanilyic acid (TGMP), which, by pseudofeedback interference with purine biosynthesis, interferes with the synthesis of guanine nucleotides. Some of its activity may also be due to the incorporation of thioguanine nucleotides into both RNA and DNA, but the end-result is inducing cell cycle arrest and apoptosis. It is metabolized via methylation by thiopurine methyltransferase.
After incorporation into DNA, the thiocarbonyl of thioguanine has a tendency to be methylated. This produces a base similar to 6-O-methylguanine.
During a second round of replication, the mismatch repair system will recognize the mismatch between the methylated base and cytosine. The attempt to repair such a mismatch is abortive since no nucleotides can be properly matched with the methylated base. This leads to persistent 100-200 base single strand breaks. Such a genotoxic stress will trigger cell cycle arrest and cell death. In this regard, thioguanine and mercaptopurine, although categorized as antimetabolites, exert their functions more like a genotoxic methylating agents, such as temozolomide, which methylates DNA and generate 6-O-methylguanine and cytosine mismatch.
The ability of thioguanine and mercaptopurine to trigger genotoxic stress is also exemplified by their treatment-related acute myeloid leukemia (AML), which is uncommon for antimetabolites, but common for alkylating agents and topoisomerase inhibitors.