WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100590
Description: Mercaptopurine is a thiopurine-derivative antimetabolite with antineoplastic and immunosuppressive activities. Produced through the metabolism of mercaptopurine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT), mercaptopurine metabolites 6-thioguanosine-5'-phosphate (6-thioGMP) and 6-thioinosine (T-IMP) inhibit nucleotide interconversions and de novo purine synthesis, thereby blocking the formation of purine nucleotides and inhibiting DNA synthesis.
MedKoo Cat#: 100590
Chemical Formula: C5H4N4S
Exact Mass: 152.01567
Molecular Weight: 152.18
Elemental Analysis: C, 39.46; H, 2.65; N, 36.82; S, 21.07
Synonym: 6-Thiohypoxanthine; 6-thiopurine; 6-mercaptopurine;
IUPAC/Chemical Name: 1H-purine-6(7H)-thione.
InChi Key: GLVAUDGFNGKCSF-UHFFFAOYSA-N
InChi Code: InChI=1S/C5H4N4S/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)
SMILES Code: S=C1NC=NC2=C1NC=N2
Mercaptopurine is used to treat leukemia. It is also used for pediatric non-Hodgkin's lymphoma, polycythemia vera, psoriatic arthritis, and inflammatory bowel disease (such as Crohn's disease and ulcerative colitis). It has demonstrated some in vitro effectiveness against Mycobacterium paratuberculosis.
PURINETHOL (mercaptopurine) was synthesized and developed by Hitchings, Elion, and associates at the Wellcome Research Laboratories. Mercaptopurine, known chemically as 1,7-dihydro-6H-purine-6-thione monohydrate, is an analogue of the purine bases adenine and hypoxanthine. PURINETHOL is available in tablet form for oral administration. Each scored tablet contains 50 mg mercaptopurine and the inactive ingredients corn and potato starch, lactose, magnesium stearate, and stearic acid.
Mechanism of action
Mercaptopurine (6-MP) competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). This intracellular nucleotide inhibits several reactions involving inosinic acid (IMP), including the conversion of IMP to xanthylic acid (XMP) and the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP). In addition, 6-methylthioinosinate (MTIMP) is formed by the methylation of TIMP. Both TIMP and MTIMP have been reported to inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. Experiments indicate that radiolabeled mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. Some mercaptopurine is converted to nucleotide derivatives of 6-thioguanine (6-TG) by the sequential actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase, converting TIMP to thioguanylic acid (TGMP). Animal tumors that are resistant to mercaptopurine often have lost the ability to convert mercaptopurine to TIMP. However, it is clear that resistance to mercaptopurine may be acquired by other means as well, particularly in human leukemias. It is not known exactly which of any one or more of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for cell death.
1: Hareedy MS, El Desoky ES, Woillard JB, Thabet RH, Ali AM, Marquet P, Picard N.
Genetic variants in 6-mercaptopurine pathway as potential factors of
hematological toxicity in acute lymphoblastic leukemia patients.
Pharmacogenomics. 2015 Aug 3:1-15. [Epub ahead of print] PubMed PMID: 26237184.