Mechanism of Action and Use of 6 – Thioguanine

6 – Thioguanine

• 6 thioguanine comes under the category of Purine antagonist antimetabolite.

• It is thio analogue of naturally occurring purine base guanine.

Structure of 6 – Thioguanine: 

IUPAC name: 2- amino-3,7 dihydro  purine -6 - thione

Mechanism of Action of 6 – Thioguanine

• 6-Thioguanine interacts with enzyme hypoxanthine-guanine phosphoribosyl transferase(HGPRTase) and gets converted into 6-thioguanosine monophosphate(TGMP).

• 6-thioguanosine monophosphate (TGMP) accumulates in the cells and inhibits the conversion of inosinic acid to xanthylic acid. This leads to the inhibition of synthesis of guanine nucleotide.

• TGMP is converted by phosphorylation to thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP).

• The TGMP, TGDP and TGTP are collectively named 6-thioguanine nucleotides (6-TGN).

• 6-TGN are cytotoxic to cells by: (1) incorporation into DNA during the synthesis phase (S-phase) of the cell.

• Thus, the effect of this drugs against the tumor cell may be due to the both actions

1. Inhibition of purine synthesis

2. As well as through induction of cytotoxicity in the cell. 

Therapeutic uses of 6 – Thioguanine:

• 6 -Thioguanine is given for the treatment of acute myelogenous leukemia (a type of cancer that begins in the white blood cells)

• It can be also used for the treatments of chronic myelogenous leukemia.