Browse history interactively

Page 1

Page 1Revision 1

Page 2

Page 2Revision 2

← Previous editContent deleted Content addedVisualWikitext

Revision as of 15:50, 14 March 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (changes to watched fields - added verified revid) per Chem/Drugbox validation (report errors or bugs)← Previous edit		Latest revision as of 16:50, 12 January 2025 edit undoArthurfragoso (talk | contribs)Extended confirmed users, Template editors4,591 edits dark mode fix
(224 intermediate revisions by more than 100 users not shown)
Line 1:		Line 1:
			{{Short description|Chemical compound}}
	{{Drugbox | Watchedfields = changed
			{{Use dmy dates|date=June 2024}}
	| verifiedrevid = 414458361
			{{cs1 config |name-list-style=vanc |display-authors=6}}
	|
			{{Infobox drug
	| IUPAC_name = 3,7-dihydropurine-6-thione
			| verifiedrevid = 462248688
	| image = Mercaptopurine.svg		| image = Mercaptopurine.svg
			| image_class = skin-invert-image
	| width = 200		| width = 200
			| image2 = Mercaptopurin ball-and-stick.png
			| image_class2 = bg-transparent
			<!--Clinical data-->
			| tradename = Purinethol, Purixan, others
			| synonyms = 6-mercaptopurine (6-MP)
			| Drugs.com = {{drugs.com|monograph|mercaptopurine}}
			| MedlinePlus = a682653
			| DailyMedID = Mercaptopurine
			| pregnancy_category =
			| routes_of_administration = ]
			| ATC_prefix = L01
			| ATC_suffix = BB02
			| legal_EU = Rx-only
			| legal_EU_comment = <ref>{{cite web | title=Xaluprine EPAR | website=European Medicines Agency | date=30 April 2009 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/xaluprine-previously-mercaptopurine-nova-laboratories | access-date=25 June 2024}}</ref>
			| legal_status = Rx-only
			<!--Pharmacokinetic data-->
			| bioavailability = 5 to 37%
			| metabolism = ]
			| elimination_half-life = 60 to 120 min., longer for its active metabolites
			| excretion = ]
			<!--Identifiers-->
			| IUPHAR_ligand = 7226
			| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 50-44-2
			| PubChem = 667490
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank = DB01033
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 580869		| ChemSpiderID = 580869
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = PKK6MUZ20G		| UNII = PKK6MUZ20G
			| KEGG_Ref = {{keggcite|correct|kegg}}
	| InChI = 1/C5H4N4S/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)
			| KEGG = D04931
	| InChIKey = GLVAUDGFNGKCSF-UHFFFAOYAL
			| ChEBI_Ref = {{ebicite|correct|EBI}}
	| smiles = S=C2/N=C\Nc1ncnc12
			| ChEBI = 50667
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 1425		| ChEMBL = 1425
			<!--Chemical data-->
			| IUPAC_name = 3,7-dihydropurine-6-thione
			| C=5 | H=4 | N=4 | S=1
			| smiles = S=c1ncc2ncc12
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C5H4N4S/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)		| StdInChI = 1S/C5H4N4S/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = GLVAUDGFNGKCSF-UHFFFAOYSA-N		| StdInChIKey = GLVAUDGFNGKCSF-UHFFFAOYSA-N
	| CAS_number = 50-44-2
	| CASNo_Ref = {{cascite|correct|CAS}}
	| ATC_prefix = L01
	| ATC_suffix = BB02
	| PubChem = 667490
	| DrugBank = APRD01096
	| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D04931
	| C = 5 | H = 4 | N = 4 | S = 1
	| molecular_weight = 152.177 g/mol
	| bioavailability = 5 to 37%
	| metabolism = ]
	| elimination_half-life = 60 to 120 min., longer for its active metabolites
	| excretion = ]
	| pregnancy_category = ?,(Increased Risk of Abortion)
	| legal_status = ?
	| routes_of_administration = Oral
	}}		}}
			<!-- Definition and medical uses -->
	'''Mercaptopurine''' (also called 6-mercaptopurine, 6-MP or its brand name '''Purinethol''') is an ].
			'''Mercaptopurine''' ('''6-MP'''), sold under the brand name '''Purinethol''' among others, is a medication used for ] and ].<ref name=AHFS2016/> Specifically it is used to treat ] (ALL), ] (APL), ], and ].<ref name=AHFS2016/><ref name=BNF69/> For acute lymphocytic leukemia it is generally used with ].<ref name=AHFS2016/> It is taken orally.<ref name=AHFS2016>{{cite web|title=Mercaptopurine|url=https://www.drugs.com/monograph/mercaptopurine.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220192655/https://www.drugs.com/monograph/mercaptopurine.html|archive-date=20 December 2016}}</ref>
			<!-- Side effects and mechanisms -->
	It is a ].<ref name="pmid18506437">{{cite journal |author=Sahasranaman S, Howard D, Roy S |title=Clinical pharmacology and pharmacogenetics of thiopurines |journal=Eur. J. Clin. Pharmacol. |volume=64 |issue=8 |pages=753–67 |year=2008 |month=August |isbn=0022800804786 |pmid=18506437 |doi=10.1007/s00228-008-0478-6}}</ref>
			Common side effects include ], ], vomiting, and loss of appetite.<ref name=AHFS2016/> Other serious side effects include an increased risk of future cancer and ].<ref name=AHFS2016/> Those with a genetic deficiency in ] are at higher risk of side effects.<ref name=AHFS2016/> Use in ] may harm the baby.<ref name=AHFS2016/> Mercaptopurine
			is in the ] and ] family of medications.<ref name=Sah2008>{{cite journal | vauthors = Sahasranaman S, Howard D, Roy S | title = Clinical pharmacology and pharmacogenetics of thiopurines | journal = European Journal of Clinical Pharmacology | volume = 64 | issue = 8 | pages = 753–67 | date = August 2008 | pmid = 18506437 | doi = 10.1007/s00228-008-0478-6 | s2cid = 27475772 }}</ref><ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=590|edition=69}}</ref>
			<!-- History and culture -->
	==Uses==
			Mercaptopurine was approved for medical use in the United States in 1953.<ref name=AHFS2016/> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>
	It is used to treat ]. It is also used for pediatric ],{{Citation needed|date=February 2009}} ],{{Citation needed|date=February 2009}} ],{{Citation needed|date=February 2009}} and ] (such as ] and ]).<ref name="pmid11683683">{{cite journal |author=Nielsen OH, Vainer B, Rask-Madsen J |title=Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine |journal=Aliment. Pharmacol. Ther. |volume=15 |issue=11 |pages=1699–708 |year=2001 |month=November |pmid=11683683 |doi= 10.1046/j.1365-2036.2001.01102.x|url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0269-2813&date=2001&volume=15&issue=11&spage=1699}}</ref>
			==Medical uses==
	It has demonstrated some in vitro effectiveness against '']''.<ref name="pmid18070971">{{cite journal |author=Shin SJ, Collins MT |title=Thiopurine drugs azathioprine and 6-mercaptopurine inhibit Mycobacterium paratuberculosis growth in vitro |journal=Antimicrob. Agents Chemother. |volume=52 |issue=2 |pages=418–26 |year=2008 |month=February |pmid=18070971 |pmc=2224720 |doi=10.1128/AAC.00678-07 |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=18070971}}</ref>
			It is used to treat ], ], and ].<ref name=AHFS2015>{{cite web|title=Mercaptopurine|url=https://www.drugs.com/monograph/mercaptopurine.html|publisher=The American Society of Health-System Pharmacists|access-date=Aug 28, 2015|url-status=live|archive-url=https://web.archive.org/web/20150906153856/http://www.drugs.com/monograph/mercaptopurine.html|archive-date=2015-09-06}}</ref>
	==Mechanisms of action==		==Side effects==
	6-MP ribonucleotide inhibits purine nucleotide synthesis and metabolism. This alters the synthesis and function of ] and ]. Mercaptopurine interferes with ] interconversion and glycoprotein synthesis.
			Some of the ]s of taking mercaptopurine may include diarrhea, nausea, vomiting, loss of appetite, fatigue, stomach/abdominal pain, weakness, skin ], darkening of the skin, and hair loss. Serious adverse reactions include mouth sores, ], ], easy bruising or bleeding, pinpoint red spots on the skin, yellowing of eyes or skin, dark ], and painful or difficult urination. Other more serious side effects include black or tarry ] (]), bloody stools, and bloody ]. Treatment is discontinued in up to 30% of patients due these effects but therapeutic drug monitoring of the biologically active metabolites, ''i.e.'' thiopurine nucleotides can help to optimize the efficacy and safety. Clinically, most hospitals resort to on-exchange LC-MS (liquid chromatography - mass spectrometry) but the newly developed approach of porous graphitic carbon based chromatography hyphenated with mass spectrometry appears superior with respect to patient care in this respect.<ref>{{cite journal | vauthors = Pecher D, Zelinkova Z, Lucenicova J, Peppelenbosch M, Dokupilova S, Mikusova V, Mikus P | title = Porous graphitic carbon based chromatography hyphenated with mass spectrometry: A new strategy for profiling thiopurine nucleotides in patients with inflammatory bowel diseases | journal = Analytica Chimica Acta | volume = 1137 | issue = 1137 | pages = 64–73 | date = November 2020 | pmid = 33153610 | doi = 10.1016/j.aca.2020.08.064 | bibcode = 2020AcAC.1137...64P | s2cid = 225287631 }}</ref>
	==Adverse reactions==
			Symptoms of allergic reaction to mercaptopurine include ], ], ], ], trouble ], and ].
	Some of the ]s of taking mercaptopurine might include diarrhea, nausea, vomiting, loss of appetite, fatigue, stomach/abdominal pain, weakness, skin ], darkening of the skin, or hair loss. Serious adverse reactions include mouth sores, ], ], easy bruising or bleeding, pinpoint red spots on the skin, yellowing of eyes or skin, dark ], painful or difficult urination. Unlikely but serious side effects include: black or tarry ] (]), bloody stools, and bloody ].
			In some cases, mercaptopurine may ], both ]s and ]s. It may be toxic to ]. Quarterly blood counts are necessary for people on mercaptopurine. People should stop taking the medication at least temporarily while considering alternate treatment if there is an unexplained, abnormally large drop in white blood cell count, or any other blood count.
	Symptoms of allergic reaction to mercaptopurine include ], ], ], ], trouble ], and ].
			Toxicity of mercaptopurine can be linked to genetic polymorphisms in ], ],<ref>{{cite journal | vauthors = Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, Pei D, Chen Y, Crews KR, Kornegay N, Wong FL, Evans WE, Pui CH, Bhatia S, Relling MV | display-authors = 6 | title = Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia | journal = Journal of Clinical Oncology | volume = 33 | issue = 11 | pages = 1235–42 | date = April 2015 | pmid = 25624441 | pmc = 4375304 | doi = 10.1200/jco.2014.59.4671 }}</ref><ref>{{cite journal | vauthors = Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA, Zhao X, Lin TN, Hoshitsuki K, Nersting J, Kihira K, Hofmann U, Komada Y, Kato M, McCorkle R, Li L, Koh K, Najera CR, Kham SK, Isobe T, Chen Z, Chiew EK, Bhojwani D, Jeffries C, Lu Y, Schwab M, Inaba H, Pui CH, Relling MV, Manabe A, Hori H, Schmiegelow K, Yeoh AE, Evans WE, Yang JJ | display-authors = 6 | title = NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity | journal = Nature Genetics | volume = 48 | issue = 4 | pages = 367–73 | date = April 2016 | pmid = 26878724 | pmc = 5029084 | doi = 10.1038/ng.3508 }}</ref> and inosine triphosphate pyrophosphatase (ITPA). People with specific allele variants will require dose adjustments, especially for those with homozygous variant genotypes. Large differences of TPMT and NUDT15 among ethnicities in terms of variant allele frequency should be taken into consideration in clinical practice.<ref>{{cite journal | vauthors = Yin D, Xia X, Zhang J, Zhang S, Liao F, Zhang G, Zhang Y, Hou Q, Yang X, Wang H, Ma Z, Wang H, Zhu Y, Zhang W, Wang Y, Liu B, Wang L, Xu H, Shu Y | display-authors = 6 | title = Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose | journal = Oncotarget | volume = 8 | issue = 8 | pages = 13575–13585 | date = February 2017 | pmid = 28088792 | pmc = 5355121 | doi = 10.18632/oncotarget.14594 }}</ref> Caucasian people with a variant allele of the ITPA gene, experience higher rates of febrile neuropenia than people of other ethnic groups, due to differences in allelic frequencies among ethnicities.<ref>{{cite journal | vauthors = Esses SI, Morley TP | title = Spinal arachnoiditis | journal = The Canadian Journal of Neurological Sciences | volume = 10 | issue = 1 | pages = 2–10 | date = February 1983 | pmid = 6404543 | doi = 10.1017/s0317167100044486 | doi-access = free }}</ref>
	Mercaptopurine causes ], suppressing the production of ]s and ]s. It may be toxic to ]. Weekly blood counts are recommended for patients on mercaptopurine. The patient should stop taking the medication at least temporarily if there is an unexplained, abnormally large drop in white blood cell count, or any other blood count.
			===Precautions===
	Patients who exhibit myelosuppression or ] toxicity should be tested for ] (TPMT) enzyme deficiency. Patients with ] are much more likely to develop dangerous myelosuppression. In such patients it may be possible to continue using mercaptopurine, but at a lower dose.
			Mercaptopurine can lower the body's ability to fight off infection. Those taking it should get permission from a doctor to receive ]s and ]s. It is also recommended that, while on the drug, one should avoid those having recently received oral ] vaccine.
			This drug was formerly not recommended during pregnancy and early evidence indicated pregnant women on the drug (or the related ]) showed a seven-fold incidence of fetal abnormalities as well as a 20-fold increase in miscarriage.<ref name=mercaptopurine_birth_outcome>{{cite journal | vauthors = Nørgård B, Pedersen L, Fonager K, Rasmussen SN, Sørensen HT | title = Azathioprine, mercaptopurine and birth outcome: a population-based cohort study | journal = Alimentary Pharmacology & Therapeutics | volume = 17 | issue = 6 | pages = 827–34 | date = March 2003 | pmid = 12641505 | doi = 10.1046/j.1365-2036.2003.01537.x | s2cid = 25314258 | doi-access = free }}</ref> There were also anecdotal reports linking mercaptopurine with spontaneous abortion, leading to the US FDA rating both AZA and mercaptopurine as category D drugs. However, Davis et al. 1999 found mercaptopurine, compared to ], was ineffective as a single-agent ]; every woman in the mercaptopurine arm of the study had fetal cardiac activity at follow-up (two weeks later) and was given a ].<ref name=useless_in_abortion>{{cite journal | vauthors = Davis AR, Miller L, Tamimi H, Gown A | title = Methotrexate compared with mercaptopurine for early induced abortion | journal = Obstetrics and Gynecology | volume = 93 | issue = 6 | pages = 904–9 | date = June 1999 | pmid = 10362152 | doi = 10.1016/S0029-7844(98)00569-9 | url = http://www.greenjournal.org/cgi/content/full/93/6/904 | url-status = live | archive-url = https://web.archive.org/web/20060619115203/http://www.greenjournal.org/cgi/content/full/93/6/904 | archive-date = 2006-06-19 }}</ref> A more recent, larger study, however, performed by the Cancers et Surrisque Associe aux Maladies inflamatoires intestinales En France (CESAME) indicated an overall rate of congenital malformations not significantly greater than the general population in France.<ref name=mercaptopurine_birth_outcome_2010>{{cite journal | vauthors = Coelho J, Beaugerie L, Colombel JF, Hébuterne X, Lerebours E, Lémann M, Baumer P, Cosnes J, Bourreille A, Gendre JP, Seksik P, Blain A, Metman EH, Nisard A, Cadiot G, Veyrac M, Coffin B, Dray X, Carrat F, Marteau P | display-authors = 6 | title = Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study | journal = Gut | volume = 60 | issue = 2 | pages = 198–203 | date = February 2011 | pmid = 21115547 | doi = 10.1136/gut.2010.222893 | s2cid = 25614617 }}</ref> The European Crohn's and Colitis Organisation (ECCO) concluded in a consensus paper in 2010 that while AZA and mercaptopurine have an FDA rating of D, new research in both animals and humans indicates that "thiopurines are safe and well tolerated during pregnancy."<ref name=ECCO_Consensus_2010>{{cite journal | vauthors = Van Assche G, Dignass A, Reinisch W, van der Woude CJ, Sturm A, De Vos M, Guslandi M, Oldenburg B, Dotan I, Marteau P, Ardizzone A, Baumgart DC, D'Haens G, Gionchetti P, Portela F, Vucelic B, Söderholm J, Escher J, Koletzko S, Kolho KL, Lukas M, Mottet C, Tilg H, Vermeire S, Carbonnel F, Cole A, Novacek G, Reinshagen M, Tsianos E, Herrlinger K, Oldenburg B, Bouhnik Y, Kiesslich R, Stange E, Travis S, Lindsay J | display-authors = 6 | title = The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations | journal = Journal of Crohn's & Colitis | volume = 4 | issue = 1 | pages = 63–101 | date = February 2010 | pmid = 21122490 | doi = 10.1016/j.crohns.2009.09.009 | doi-access = free }}</ref>
			Mercaptopurine causes changes to ]s in animals and humans, though a study in 1990<ref name=6mp_in_mice>{{cite journal | vauthors = Maekawa A, Nagaoka T, Onodera H, Matsushima Y, Todate A, Shibutani M, Ogasawara H, Kodama Y, Hayashi Y | display-authors = 6 | title = Two-year carcinogenicity study of 6-mercaptopurine in F344 rats | journal = Journal of Cancer Research and Clinical Oncology | volume = 116 | issue = 3 | pages = 245–50 | date = May 1990 | pmid = 2370249 | doi = 10.1007/BF01612898 | s2cid = 21675626 }}</ref> found, "while the carcinogenic potential of 6-MP cannot be precluded, it can be only very weak or marginal." Another study in 1999<ref name=6mp_and_leukemia>{{cite journal | vauthors = Bo J, Schrøder H, Kristinsson J, Madsen B, Szumlanski C, Weinshilboum R, Andersen JB, Schmiegelow K | display-authors = 6 | title = Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism | journal = Cancer | volume = 86 | issue = 6 | pages = 1080–6 | date = September 1999 | pmid = 10491537 | doi = 10.1002/(SICI)1097-0142(19990915)86:6<1080::AID-CNCR26>3.0.CO;2-5 | s2cid = 45441636 | doi-access = free }}</ref> noted an increased risk of developing leukemia when taking large doses of 6-MP with other ] drugs.
	== Drug interactions ==		== Drug interactions ==
	Allopurinol inhibits ], the enzyme that breaks down mercaptopurine. Those who take ] (often used to prevent gout) are at risk for mercaptopurine toxicity. The dose should be reduced or allopurinol should be discontinued.		Allopurinol inhibits ], the enzyme that breaks down mercaptopurine. Those taking ] (often used to prevent gout) are at risk for mercaptopurine toxicity. The dose should be reduced or allopurinol should be discontinued.
			Several published studies have demonstrated that the use of allopurinol in combination with low dose 6-MP helps reduce 6-MP levels, which are toxic to liver tissue, whilst increasing the therapeutic levels of 6-MP for some inflammatory conditions.
			==Mechanisms of action==
	==Precautions==
			{{Technical|section|date=December 2014}}
			Official information from the package insert for purinethol:<ref>{{cite web|title=PURINETHOL (mercaptopurine) tablet |work=DailyMed|publisher=Gate Pharmaceuticals|date=August 2012|url=http://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=f9af557d-37bf-4078-888e-37c086dfc6e9&type=pdf&name=f9af557d-37bf-4078-888e-37c086dfc6e9|format=PDF|access-date=31 December 2013|url-status=live|archive-url=https://web.archive.org/web/20140101024906/http://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=f9af557d-37bf-4078-888e-37c086dfc6e9&type=pdf&name=f9af557d-37bf-4078-888e-37c086dfc6e9|archive-date=1 January 2014}}</ref>
			*Mercaptopurine is an antimetabolite antineoplastic; as such it interferes with normal metabolic processes within cells, typically by combining with enzymes, to disrupt DNA and RNA synthesis (cell-cycle S phase-specific) leading to death of rapidly proliferating cells, especially malignant ones. Specifically, Mercaptopurine is a purine antimetabolite or purine antagonist and as such inhibits DNA synthesis by inhibiting the production of the purine containing nucleotides, adenine and guanine, thus halting DNA synthesis.<ref>{{Cite web|url=https://www.cancerquest.org/patients/treatments/chemotherapy#purine|title = Chemotherapy}}</ref> Mercaptopurine also acts as an immunomodulator by inhibiting several pathways in nucleic acid biosynthesis preventing proliferation of cells involved in the determination and amplification of the immune response.<ref>Nielsen OH, Vainer B, Rask-Madsen J. Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine. Aliment Pharmacol Ther. 2001 Nov;15(11):1699-708. doi: 10.1046/j.1365-2036.2001.01102.x. PMID 11683683.</ref>
			*Mercaptopurine (6-MP) competes with the ] derivatives ] and ] for the enzyme ] and is itself converted to thioinosine monophosphate (TIMP).
			**TIMP inhibits several chemical reactions involving ] (IMP), including the conversion of IMP to ] (XMP) and the conversion of IMP to ] (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.
			6-MP ribonucleotide inhibits purine nucleotide synthesis and metabolism by inhibiting an enzyme called ] (PRPP amidotransferase). Since this enzyme is the rate limiting factor for purine synthesis,<ref>Hansen, Barbara. "Purine and Pyrimidine Metabolism." USMLE STEP 1 Biochemistry and Medical Genetics Lecture Notes. 2010 ed. N.p.: Kaplan, 2010. 288-90. Print.</ref> this alters the synthesis and function of ] and ].{{Citation needed|date=March 2013}} Mercaptopurine interferes with ] interconversion and glycoprotein synthesis.
	Mercaptopurine can lower the body's ability to fight off infection. Those taking mercaptopurine should get permission from a doctor in order to receive ]s and ]s. It is also recommended that while on the drug one should avoid those who have recently received oral ] vaccine.
			===Pharmacogenetics===
	This drug is traditionally not recommended during pregnancy but this issue has been debated and current evidence indicates that pregnant women on the drug show no increase in fetal abnormalities. However, women receiving mercaptopurine during the first trimester of pregnancy have an increased incidence of miscarriage {{Citation needed|date=April 2010}}. Davis et al. 1999 found that mercaptopurine, compared to ], was ineffective as a single-agent abortifacient; every woman in the mercaptopurine arm of the study had fetal cardiac activity at follow-up (two weeks later) and was given a suction abortion.<ref name=useless_in_abortion>{{cite journal | first = Anne R. | last = Davis | coauthors = Leslie Miller, Hisham Tamimi, and Allen Gown | year = 1999 | month = June | title = Methotrexate Compared With Mercaptopurine for Early Induced Abortion | journal = Obstetrics & Gynecology | volume = 93 | issue = 6 | pages = 904–9 | pmid = 10362152 | url = http://www.greenjournal.org/cgi/content/full/93/6/904 | doi = 10.1016/S0029-7844(98)00569-9}}</ref>
			The enzyme ] (TPMT) is responsible, in part, for the inactivation of 6-mercaptopurine. TPMT catalyzes the ] of 6-mercaptopurine into the inactive metabolite 6-methylmercaptopurine – this ] prevents mercaptopurine from further conversion into active, ] thioguanine nucleotide (TGN) metabolites.<ref name="pmid19952870">{{cite journal | vauthors = Zaza G, Cheok M, Krynetskaia N, Thorn C, Stocco G, Hebert JM, McLeod H, Weinshilboum RM, Relling MV, Evans WE, Klein TE, Altman RB | display-authors = 6 | title = Thiopurine pathway | journal = Pharmacogenetics and Genomics | volume = 20 | issue = 9 | pages = 573–4 | date = September 2010 | pmid = 19952870 | pmc = 3098750 | doi = 10.1097/FPC.0b013e328334338f }}</ref><ref name="pmid24707136">{{cite journal | vauthors = Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G | display-authors = 6 | title = Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? | journal = World Journal of Gastroenterology | volume = 20 | issue = 13 | pages = 3534–41 | date = April 2014 | pmid = 24707136 | pmc = 3974520 | doi = 10.3748/wjg.v20.i13.3534 | doi-access = free }}</ref><ref name="pmid17691917">{{cite journal | vauthors = Fujita K, Sasaki Y | title = Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy | journal = Current Drug Metabolism | volume = 8 | issue = 6 | pages = 554–62 | date = August 2007 | pmid = 17691917 | doi = 10.2174/138920007781368890 | url = http://www.bentham-direct.org/pages/content.php?CDM/2007/00000008/00000006/0002F.SGM | url-status = usurped | archive-url = https://archive.today/20130112103320/http://www.bentham-direct.org/pages/content.php?CDM/2007/00000008/00000006/0002F.SGM | archive-date = 2013-01-12 }}</ref> Certain ]s within the TPMT gene can lead to decreased or absent TPMT enzyme activity, and individuals who are ] or ] for these types of ]s may have increased levels of TGN metabolites and an increased risk of severe bone marrow suppression (]) when receiving mercaptopurine.<ref name="pmid21270794">{{cite journal | vauthors = Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Klein TE | display-authors = 6 | title = Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing | journal = Clinical Pharmacology and Therapeutics | volume = 89 | issue = 3 | pages = 387–91 | date = March 2011 | pmid = 21270794 | pmc = 3098761 | doi = 10.1038/clpt.2010.320 }}</ref> In many ethnicities, ''TPMT'' polymorphisms that result in decreased or absent TPMT activity occur with a frequency of approximately 5%, meaning that about 0.25% of people are ] for these variants.<ref name="pmid21270794"/><ref name="Mutschler">{{Cite book| vauthors = Mutschler E, Schäfer-Korting M |title=Arzneimittelwirkungen|pages = 107, 936|language=de|location=Stuttgart|publisher=Wissenschaftliche Verlagsgesellschaft|year=2001|edition=8th|isbn=978-3-8047-1763-3}}</ref> However, an assay of TPMT activity in ]s or a TPMT ] can identify people with reduced TPMT activity, allowing for the adjustment of mercaptopurine dose or avoidance of the drug entirely.<ref name="pmid21270794"/><ref>{{cite journal | vauthors = Payne K, Newman W, Fargher E, Tricker K, Bruce IN, Ollier WE | title = TPMT testing in rheumatology: any better than routine monitoring? | journal = Rheumatology | volume = 46 | issue = 5 | pages = 727–9 | date = May 2007 | pmid = 17255139 | doi = 10.1093/rheumatology/kel427 | doi-access = free }}</ref> The FDA-approved drug label for mercaptopurine recommends testing for TPMT activity to identify people at risk for ].<ref>{{cite web|url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=15904472-4c32-4224-95d3-eb131a7ff9c8|title=Label: Mercaptopurine – mercaptopurine tablet|access-date=11 March 2015|url-status=live|archive-url=https://web.archive.org/web/20151006122006/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=15904472-4c32-4224-95d3-eb131a7ff9c8|archive-date=6 October 2015}}</ref><ref>{{cite web | title=Purixan suspension | website=DailyMed | date=9 April 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9fd27952-7787-47d9-b6cf-7af2dc38217b | access-date=9 April 2020}}</ref> Testing for TPMT activity is an example of ] being translated into routine clinical care.<ref name="pmid20154640">{{cite journal | vauthors = Wang L, Pelleymounter L, Weinshilboum R, Johnson JA, Hebert JM, Altman RB, Klein TE | title = Very important pharmacogene summary: thiopurine S-methyltransferase | journal = Pharmacogenetics and Genomics | volume = 20 | issue = 6 | pages = 401–5 | date = June 2010 | pmid = 20154640 | pmc = 3086840 | doi = 10.1097/FPC.0b013e3283352860 }}</ref>
	Mercaptopurine causes changes to ]s in animals and humans, though a study in 1990<ref name=6mp_in_mice>{{cite journal | first = A. | last = Maekawa | coauthors = T. Nagaoka, H. Onodera, Y. Matsushima, A. Todate, M. Shibutani, H. Ogasawara, Y. Kodama and Y. Hayashi | year = 1990 | month = May | title = Two-year carcinogenicity study of 6-mercaptopurine in F344 rats | journal = Journal of Cancer Research and Clinical Oncology | volume = 116 | issue = 3 | pages = 245–250 | pmid = 2370249 | url = http://www.springerlink.com/content/k28hxj615p761764/ | doi = 10.1007/BF01612898}}</ref> found that "while the carcinogenic potential of 6-MP can not be precluded, it can be only very weak or marginal." Another study in 1999<ref name=6mp_and_leukemia>{{cite journal |author=Bo J, Schrøder H, Kristinsson J, Madsen B, Szumlanski C, Weinshilboum R, Andersen JB, Schmiegelow K |title=Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism |journal=Cancer |volume=86 |issue=6 |pages=1080–6 |year=1999 |month=September |pmid=10491537|doi=10.1002/(SICI)1097-0142(19990915)86:6<1080::AID-CNCR26>3.0.CO;2-5}}</ref> noted an increased risk of developing leukemia when taking large doses of 6-MP together with other ] drugs.
	==See also==		==History==
			6-MP was discovered by Nobel Prize–winning scientists ] and ] at ] in ],<ref>{{cite web | vauthors = Bouton K | work = The New York Times Magazine | date = 29 January 1989 | url = https://www.nytimes.com/1989/01/29/magazine/the-nobel-pair.html | title = The Nobel Pair | archive-url = https://web.archive.org/web/20161007121620/http://www.nytimes.com/1989/01/29/magazine/the-nobel-pair.html | archive-date=2016-10-07 }}</ref> and was clinically developed in collaboration with investigators at Memorial Hospital (now ] in New York City).<ref name=Emp>{{cite book |vauthors=Mukherjee S |date=2010 |title=The Emperor of All Maladies: A Biography of Cancer |location=New York |publisher=Scribner |pages=91–92 |isbn=978-1439170915}}</ref> The collaboration was initiated by ], who had run ] programs for the US Army and had been involved in the work that led to the discovery that ]s could potentially be used as cancer drugs, and had become the director of Memorial in 1948.<ref name=Emp/>
	*]
	==References==		== References ==
	{{Reflist|2}}		{{reflist}}
			== Further reading ==
	==External links==
			* {{cite book | title=Medical Genetics Summaries | chapter=Mercaptopurine Therapy and TPMT Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK100660/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=] (NCBI) | year=2012 | pmid=28520348 | id=Bookshelf ID: NBK100660 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}
	*
	{{Chemotherapeutic agents}}		{{Chemotherapeutic agents}}
			{{Portal bar | Medicine}}
			{{Authority control}}
	]
	]		]
	]		]
			]
			]
	]
			]
	]
			]
	]
	]
	]
	]
	]
	]
	]