6-MERCAPTOPURINE

Healthconcerns “Articles on cancer” is going to add a complete pharmacology and the medicinal chemistry of the Anti-cancer drugs. So here is the first one as “6-MERCAPTOPURINE”

6-Mercaptopurine

Chemical structure

Chemically 6-Mercaptopurine is analog of adenine and hypoxanthine  

                                              

Mechanism of action

6-Mercaptupurine is converted to   6- Mercaptopurine nucleosides leading to De novo inhibition of purine nucleotide synthesis.

¨      6-Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine/guanine phosphoribosyltransferase  and itself converted to thioinosinic acid

                                                                     Inosinic acid (I) MP 

          

                                                                    Thioinosinic acid (I MP)
 

¨      TIMP inhibits several reactions involving inosinic mono phosphate (IMP) including its conversion to xanthylic acid and adenylic acid

¨      Thioinosinic mono phosphate on methylation is converted into 6-methylthinosinate

¨      Both TIMP and 6-methylthinosinate inhibit glutamine phosphoribosyl pyrophosphate amidotransferase, involved in purine ribonucleotide synthesis

Chemical synthesis

Pharmacokinetics

•         Rapidly absorbed when administered orally- maximum level is achived within 1-2 h after administration

•         Distributed in all tissues except the brain because it cannot cross blood–brain barrier

Metabolism

Three enzymes play major role in the metabolism of mercaptopurine   

1-     Xanthine oxidase

2-     Thiopurine methyltransferase

3-     hypoxanthine/guanine 

        phosphoribosyltransferase

¨      Degradation is primarily by xanthine oxidase. Urine contains intact mercaptopurine, thiouric acid and a number of 6-methylated thiopurines

¨      The methylthiopurines yield appreciable amount of inorganic sulphate

Excretion

The parent drug and its metabolites are excreted by the kidney

Uses

Widely used as an adjunctive immunosuppressive agent, in patients gastroenterology (chronic bowel syndrome)

It is also a corticosteroid-sparing agent having organ transplants, and in rheumatology, dermatology.