Thioguanine is catabolized ( broken down ) via two pathways.
2.
The thiopurines include thioguanine and mercaptopurine.
3.
Thioguanine is excreted primarily through the kidneys in urine, but mainly as a metabolite, 2-amino-6-methylthiopurine.
4.
Thioguanine cannot be demonstrated in cerebrospinal fluid, similar to the closely related compound 6-mercaptopurine which also cannot penetrate to the brain.
5.
TPMT is best known for its role in the metabolism of the thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine.
6.
Thioguanine is incorporated into human bone marrow cells, but like other thiopurines, it is not known to cross the blood-brain barrier.
7.
Thiopurine methyltransferase ( TPMT ) catalyzes the S-methylation of thiopurines, thereby regulating the balance between cytotoxic thioguanine nucleotide and inactive metabolites in hematopoietic cells.
8.
An additional effect may be derived from the incorporation of 6-thioguanine into RNA . This yields a modified RNA strand which cannot be read by the ribosomes.
9.
It is inhibited by Mycophenolic acid, ribavirin, and 6TGMP ( 6-thioguanine monophosphate ) . 6TGMP inhibition prevents purine interconversion and thus the synthesis of purine nucleotides.
10.
Thioguanine, like other thiopurines, is cytotoxic to white cells; as a result it is immunosuppressive at lower doses and anti-leukemic / anti-neoplastic at higher doses.
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