Mercaptopurine

Structural formula
General
Non-proprietary name	Mercaptopurine
other names	7 H -purine-6-thiol
Molecular formula	C 5 H 4 N 4 S
Brief description	yellow crystalline powder
External identifiers / databases
EC number	200-037-4
ECHA InfoCard	100,000,035
PubChem	667490
ChemSpider	580869
DrugBank	DB01033
Wikidata	Q418529
Drug information
ATC code	L01 BB02
Drug class	Antimetabolite , cytostatic agent
properties
Molar mass	152.18 g · mol -1
Physical state	firmly
Melting point	313-314 ° C (decomposition)
solubility	practically insoluble in water; soluble in methanol ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 301-341-361fd
	P: 280-301 + 330 + 331 + 310
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Mercaptopurine ( INN ), also 6-mercaptopurine ( 6-MP ), is an analogue of the nucleobases adenine and guanine . It is used as a cytostatic agent in the chemotherapy of leukemia , as well as for the long-term therapy of chronic intestinal inflammation . Mercaptopurine was patented by Burroughs Wellcome in 1955 . Monohydrate is sometimes used as a medicinal substance .

pharmacology

Mercaptopurine is an antimetabolite , which means that it is incorporated into the DNA instead of the purine bases adenine and guanine during cell division . The resulting DNA then loses its function.

6-mercaptopurine is produced from the prodrug azathioprine by metabolism in the liver . At the same time, the effect of 6-mercaptopurine can be increased by inhibiting its breakdown by the uricostatic allopurinol . This allows lower dosages to be used, which cause fewer undesirable side effects.

Mercaptopurine is often tolerated if azathioprine is intolerant. While in Germany azathioprine is initially used to treat chronic intestinal inflammation, in the USA, for example, mercaptopurine is used almost exclusively.

Pharmacogenetics

Mercaptopurine is metabolized in a two-step process by the enzymes thiopurine methyltransferase (TPMT) and xanthine oxidase . The TPMT shows a relevant polymorphism in humans. About 10% of the population show a significantly reduced enzyme activity and about 0.3% show no detectable TPMT activity at all. These patients can experience unexpectedly high toxicities when mercaptopurine is administered in “normal” doses. Blood formation is particularly affected, where pronounced cytopenia ( leukopenia , anemia , thrombopenia ) can occur. The cause of the reduced or absent enzyme activity are mutations in the gene for TPMT. Three alleles (TPMT * 2, * 3A and * 3C) are responsible for about 80-95% of cases of decreased TPMT activity. The TPMT activity is usually determined diagnostically in the erythrocytes , so this test should be carried out before the patient has received a blood transfusion , as the enzyme activity can then be false normal.

Isomerism

The chemical formula of mercaptopurine can be represented in several tautomeric boundary structures.

Trade names

Puri Nethol 50mg (EU), MERCAPTOPURIN Medice 10 mg (EU), Purinethol (D, USA), Xaluprine (D)

Individual evidence

↑ ^a ^b ^c ^d Entry on mercaptopurine. In: Römpp Online . Georg Thieme Verlag, accessed on June 13, 2013.
↑ ^a ^b ^c Entry on 6-mercaptopurine in the GESTIS substance database of the IFA , accessed on January 9, 2019(JavaScript required) .
^ S. Zhou: Clinical pharmacogenomics of thiopurine S-methyltransferase. In: Curr. Clin. Pharmacol. , Volume 1, No. 1, 2006, pp. 119-128. PMID 18666383 .

[roempp-1] Entry on mercaptopurine. In: Römpp Online . Georg Thieme Verlag, accessed on June 13, 2013.

[GESTIS-2] Entry on 6-mercaptopurine in the GESTIS substance database of the IFA , accessed on January 9, 2019(JavaScript required) .

[3] S. Zhou: Clinical pharmacogenomics of thiopurine S-methyltransferase. In: Curr. Clin. Pharmacol. , Volume 1, No. 1, 2006, pp. 119-128. PMID 18666383 .