Identification

Name
Mercaptopurine
Accession Number
DB01033  (APRD01096)
Type
Small Molecule
Groups
Approved
Description

An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. [PubChem]

Structure
Thumb
Synonyms
  • 6 MP
  • 6-Mercaptopurine
  • 6-MP
  • 6-Thiohypoxanthine
  • 6-Thioxopurine
  • Mercaptopurina
  • Mercaptopurine anhydrous
  • mercaptopurinum
  • Mercapurin
Product Ingredients
IngredientUNIICASInChI Key
Mercaptopurine monohydrateE7WED276I56112-76-1WFFQYWAAEWLHJC-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MercaptopurineTablet50 mg/1OralQuinn Pharmaceuticals, Llc2016-10-05Not applicableUs
Mercaptopurine Tablets USPTablet50 mgOralSterimax Inc2013-11-27Not applicableCanada
PurinetholTablet50 mgOralTeva1954-12-31Not applicableCanada
PurixanSuspension20 mg/mLOralNova Laboratories Limited2014-04-28Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MercaptopurineTablet50 mg/1OralMylan Pharmaceuticals2005-07-14Not applicableUs00378 3547 52 nlmimage10 8046c026
MercaptopurineTablet50 mg/1OralPhysicians Total Care, Inc.2005-05-23Not applicableUs
MercaptopurineTablet50 mg/1OralWest Ward Pharmaceutical2004-02-13Not applicableUs00054 4581 11 nlmimage10 fe3c7f73
MercaptopurineTablet50 mg/1OralRemedy Repack2011-11-032016-12-09Us
MercaptopurineTablet50 mg/1OralAvera Mc Kennan Hospital2015-03-01Not applicableUs
MercaptopurineTablet50 mg/1OralPar Pharmaceutical2004-02-11Not applicableUs49884 0922 02 nlmimage10 5e08af65
MercaptopurineTablet50 mg/1OralAmerincan Health Packaging2013-03-152015-12-29Us
International/Other Brands
Leukerin
Categories
UNII
PKK6MUZ20G
CAS number
50-44-2
Weight
Average: 152.177
Monoisotopic: 152.015666838
Chemical Formula
C5H4N4S
InChI Key
GLVAUDGFNGKCSF-UHFFFAOYSA-N
InChI
InChI=1S/C5H4N4S/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)
IUPAC Name
6,7-dihydro-3H-purine-6-thione
SMILES
S=C1N=CNC2=C1NC=N2

Pharmacology

Indication

For remission induction and maintenance therapy of acute lymphatic leukemia.

Structured Indications
Pharmacodynamics

Mercaptopurine is one of a large series of purine analogues which interfere with nucleic acid biosynthesis and has been found active against human leukemias. It is an analogue of the purine bases adenine and hypoxanthine. 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.

Mechanism of action

Mercaptopurine 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).

TargetActionsOrganism
AHypoxanthine-guanine phosphoribosyltransferase
inhibitor
Human
UAmidophosphoribosyltransferaseNot AvailableHuman
UInosine-5'-monophosphate dehydrogenase
inhibitor
Human
Absorption

Clinical studies have shown that the absorption of an oral dose of mercaptopurine in humans is incomplete and variable, averaging approximately 50% of the administered dose. The factors influencing absorption are unknown.

Volume of distribution

The volume of distribution exceeded that of the total body water.

Protein binding

Plasma protein binding averages 19% over the concentration range 10 to 50 µg/mL (a concentration only achieved by intravenous administration of mercaptopurine at doses exceeding 5 to 10 mg/kg).

Metabolism

Hepatic. Degradation primarily by xanthine oxidase. The catabolism of mercaptopurine and its metabolites is complex. In humans, after oral administration of 35S-6-mercaptopurine, urine contains intact mercaptopurine, thiouric acid (formed by direct oxidation by xanthine oxidase, probably via 6-mercapto-8-hydroxypurine), and a number of 6-methylated thiopurines. The methylthiopurines yield appreciable amounts of inorganic sulfate.

Route of elimination
Not Available
Half life

Triphasic: 45 minutes, 2.5 hours, and 10 hours.

Clearance
Not Available
Toxicity

Signs and symptoms of overdosage may be immediate such as anorexia, nausea, vomiting, and diarrhea; or delayed such as myelosuppression, liver dysfunction, and gastroenteritis. The oral LD50 of mercaptopurine was determined to be 480 mg/kg in the mouse and 425 mg/kg in the rat.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Azathioprine Metabolism PathwayDrug metabolism
Azathioprine Action PathwayDrug action
Mercaptopurine Metabolism PathwayDrug metabolism
Mercaptopurine Action PathwayDrug action
Thioguanine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Thiopurine S-methyltransferaseTPMT*2(G;G) / (C;G)G AlleleADR Directly StudiedPatients with this genotype have reduced metabolism of mercaptopurine resulting in increased toxicity.Details
Thiopurine S-methyltransferaseTPMT*3A(A;A) / (A;G)A AlleleADR Directly StudiedPatients with this genotype have reduced metabolism of mercaptopurine resulting in increased toxicity.Details
Thiopurine S-methyltransferaseTPMT*3C(G;G) / (A;G)G AlleleADR Directly StudiedPatients with this genotype have reduced metabolism of mercaptopurine resulting in increased toxicity.Details
Thiopurine S-methyltransferaseTPMT*3BNot Availablec.460G>AADR InferredMyelosuppressionDetails
Thiopurine S-methyltransferaseTPMT*4ANot AvailableG > AADR InferredMyelosuppressionDetails

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolMercaptopurine may decrease the anticoagulant activities of Acenocoumarol.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Mercaptopurine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Mercaptopurine.Experimental
AllopurinolThe serum concentration of Mercaptopurine can be increased when it is combined with Allopurinol.Approved
AzathioprineAzathioprine may increase the myelosuppressive activities of Mercaptopurine.Approved
BalsalazideThe metabolism of Mercaptopurine can be decreased when combined with Balsalazide.Approved, Investigational
BCG vaccineThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with BCG vaccine.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Mercaptopurine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Mercaptopurine.Approved
ClorindioneMercaptopurine may decrease the anticoagulant activities of Clorindione.Experimental
ClozapineThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with Clozapine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Mercaptopurine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Mercaptopurine.Experimental
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Mercaptopurine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Mercaptopurine.Approved
DicoumarolMercaptopurine may decrease the anticoagulant activities of Dicoumarol.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Mercaptopurine.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Mercaptopurine.Approved
DiphenadioneMercaptopurine may decrease the anticoagulant activities of Diphenadione.Experimental
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Mercaptopurine.Approved, Investigational
DoxorubicinDoxorubicin may increase the hepatotoxic activities of Mercaptopurine.Approved, Investigational
Ethyl biscoumacetateMercaptopurine may decrease the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FebuxostatThe serum concentration of Mercaptopurine can be increased when it is combined with Febuxostat.Approved
FingolimodMercaptopurine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FluindioneMercaptopurine may decrease the anticoagulant activities of Fluindione.Investigational
G17DTThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Mercaptopurine is combined with GI-5005.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Mercaptopurine.Experimental
INGN 201The risk or severity of adverse effects can be increased when Mercaptopurine is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Mercaptopurine is combined with INGN 225.Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Mercaptopurine.Experimental
LeflunomideThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with Leflunomide.Approved, Investigational
MesalazineThe metabolism of Mercaptopurine can be decreased when combined with Mesalazine.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Mercaptopurine.Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Mercaptopurine.Experimental
NatalizumabThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with Natalizumab.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Mercaptopurine.Experimental
OlsalazineThe metabolism of Mercaptopurine can be decreased when combined with Olsalazine.Approved
OuabainOuabain may decrease the cardiotoxic activities of Mercaptopurine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Mercaptopurine.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Mercaptopurine.Experimental
PhenindioneMercaptopurine may decrease the anticoagulant activities of Phenindione.Approved
PhenprocoumonMercaptopurine may decrease the anticoagulant activities of Phenprocoumon.Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Mercaptopurine.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Mercaptopurine.Experimental
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Mercaptopurine.Approved
RindopepimutThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with Rindopepimut.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Mercaptopurine.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Mercaptopurine.Approved
SRP 299The risk or severity of adverse effects can be increased when Mercaptopurine is combined with SRP 299.Investigational
SulfamethoxazoleSulfamethoxazole may increase the myelosuppressive activities of Mercaptopurine.Approved
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mercaptopurine.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Mercaptopurine is combined with TG4010.Investigational
TioclomarolMercaptopurine may decrease the anticoagulant activities of Tioclomarol.Experimental
TofacitinibMercaptopurine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Mercaptopurine.Approved, Investigational
TrimethoprimTrimethoprim may increase the myelosuppressive activities of Mercaptopurine.Approved, Vet Approved
WarfarinMercaptopurine may decrease the anticoagulant activities of Warfarin.Approved
Food Interactions
  • Preferably on an empty stomach, drink plenty of liquids, avoid alcohol.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15167
KEGG Drug
D04931
KEGG Compound
C02380
ChemSpider
580869
BindingDB
50423778
ChEBI
94796
ChEMBL
CHEMBL1425
Therapeutic Targets Database
DAP000147
PharmGKB
PA450379
HET
PM6
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mercaptopurine
ATC Codes
L01BB02 — Mercaptopurine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3bgd / 3ns1
FDA label
Download (44.1 KB)
MSDS
Download (73.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B-cell Adult Acute Lymphoblastic Leukemia / Lymphoma, Lymphoblastic / T-cell Adult Acute Lymphoblastic Leukemia1
1SuspendedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1, 2CompletedTreatmentAcute Undifferentiated Leukemia (AUL) / B-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / L1 Adult Acute Lymphoblastic Leukemia / L1 Childhood Acute Lymphoblastic Leukemia / L2 Adult Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia / Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia / T-cell Adult Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
1, 2TerminatedTreatmentCrohn's Disease (CD)1
2Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)2
2Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Untreated Adult Acute Lymphoblastic Leukemia1
2Active Not RecruitingTreatmentDe Novo / Low-dose Corticosteroids Pretreatment / Secondary / Untreated Philadelphia Positive Acute Lymphoblastic Leukemia1
2Active Not RecruitingTreatmentLeukaemia, Lymphoblastic / Lymphoma, Lymphoblastic1
2Active Not RecruitingTreatmentLeukemias1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL)1
2CompletedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Oligodendroglioma (AO) / Glioblastoma Multiforme / Mixed Gliomas / Recurrent Brain Tumors1
2CompletedTreatmentCancer, Breast / Cancer, Ovarian1
2CompletedTreatmentLeukemia, Lymphocytic, Acute1
2CompletedTreatmentLeukemias11
2CompletedTreatmentLeukemias / Malignant Lymphomas1
2CompletedTreatmentLeukemias / Neutropenias / Thrombocytopenias1
2CompletedTreatmentRecurrent Childhood Acute Lymphoblastic Leukemia1
2Enrolling by InvitationTreatmentAcute,Leukemia, Lymphoid1
2Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Childhood Cancers / Down Syndrome (DS)1
2RecruitingTreatmentAcute Leukemias of Ambiguous Lineage / Childhood B Acute Lymphoblastic Leukemia / KMT2A Gene Rearrangement / Mixed Phenotype Acute Leukemia (MPAL)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / Philadelphia Chromosome Positive / Recurrent Adult Acute Lymphoblastic Leukemia / Refractory Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia, B-Cell / Leukemia, T-Cell / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias1
2RecruitingTreatmentAll1
2RecruitingTreatmentB-cell Acute Lymphoblastic Leukemia1
2RecruitingTreatmentLeukaemia, Lymphoblastic1
2RecruitingTreatmentLeukemias2
2RecruitingTreatmentRecurrent B-Cell Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood B-Lymphoblastic Lymphoma1
2TerminatedTreatmentAcute Lymphocytic Leukemia (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Mixed Lineage Acute Leukemia1
2TerminatedTreatmentLeukemias / Lymphoma, Lymphoblastic / Malignant Lymphomas / Precursor-B Acute Lymphoblastic Leukemia1
2TerminatedTreatmentLymphoma, Lymphoblastic1
2TerminatedTreatmentRecurrent Adult Acute Lymphoblastic Leukemia1
2Unknown StatusTreatmentLeukemias2
2Unknown StatusTreatmentLymphoblastic Leukemia, Acute1
2WithdrawnTreatmentColitis / Cytokines / Drug Evaluation / Hermanski-Pudlak Syndrome / Lymphocytes1
2, 3CompletedTreatmentAdult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
2, 3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Lymphoma1
2, 3RecruitingTreatmentLangerhans Cell Histiocytosis (LCH)1
2, 3RecruitingTreatmentLeukemias1
2, 3RecruitingTreatmentLymphoma, Lymphoblastic1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult T Acute Lymphoblastic Leukemia / Childhood T Acute Lymphoblastic Leukemia / Stage II Adult T-Cell Leukemia/Lymphoma / Stage II Childhood Lymphoblastic Lymphoma / Stage II Contiguous Adult Lymphoblastic Lymphoma / Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Adult T-Cell Leukemia/Lymphoma / Stage III Childhood Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentAcute Undifferentiated Leukemia (AUL) / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentB-cell Childhood Acute Lymphoblastic Leukemia / Intermediate Risk Recurrent Childhood Acute Lymphoblastic Leukemia / L1 Childhood Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentB-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentChildhood Acute Promyelocytic Leukemia (M3) / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3Active Not RecruitingTreatmentDrug/Agent Toxicity by Tissue/Organ / Leukemias1
3Active Not RecruitingTreatmentLeukemias3
3Active Not RecruitingTreatmentLymphoblastic Leukemia, Acute1
3Active Not RecruitingTreatmentMalignant Lymphomas1
3CompletedSupportive CareCardiac Toxicity / Leukemias / Malignant Lymphomas1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)2
3CompletedTreatmentAdult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Promyelocytic Leukemia (M3) / Childhood Acute Promyelocytic Leukemia (M3) / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3CompletedTreatmentChildhood Acute Lymphoblastic Leukemia in Remission / Recurrent Childhood Acute Lymphoblastic Leukemia1
3CompletedTreatmentLeukemia, Myelocytic, Acute1
3CompletedTreatmentLeukemias12
3CompletedTreatmentLeukemias / Malignant Lymphomas2
3CompletedTreatmentMalignant Lymphomas2
3Not Yet RecruitingTreatmentUlcerative Colitis (UC)1
3RecruitingSupportive CareChildhood Acute Lymphoblastic Leukemia in Remission1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / BCR/ABL1 Fusion Protein Negative / Untreated Adult Acute Lymphoblastic Leukemia1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult T Acute Lymphoblastic Leukemia / Childhood T Acute Lymphoblastic Leukemia / Stage II Adult Lymphoblastic Lymphoma / Stage II Childhood Lymphoblastic Lymphoma / Stage II Contiguous Adult Lymphoblastic Lymphoma / Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Childhood Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / BCR-ABL1 Fusion Protein Expression / Minimal Residual Disease / Philadelphia Chromosome Positive / T Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
3RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3RecruitingTreatmentAcute Promyelocytic Leukemia (APL)1
3RecruitingTreatmentAdult B Lymphoblastic Lymphoma / Childhood B Acute Lymphoblastic Leukemia / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Childhood B Lymphoblastic Lymphoma / Down Syndrome (DS) / Stage I B Lymphoblastic Lymphoma / Stage II B Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Cognitive Side Effects of Cancer Therapy / Neurotoxicity Syndrome / Osteonecrosis / Pain / Testicular Leukemia / Therapy-Related Toxicity / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia1
3SuspendedTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Cognitive Side Effects of Cancer Therapy / Neurotoxicity Syndrome / Osteonecrosis / Pain / Ph-Like Acute Lymphoblastic Leukemia / Testicular Leukemia / Therapy-Related Toxicity / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3TerminatedTreatmentMalignant Lymphomas1
3Unknown StatusDiagnosticLeukemias / Myelodysplastic/Myeloproliferative Neoplasms1
3Unknown StatusPreventionCrohn's Disease (CD)1
3Unknown StatusTreatmentLeukemias3
3Unknown StatusTreatmentLeukemias / Malignant Lymphomas1
3Unknown StatusTreatmentLeukemias / Mucositis / Oral Complications1
3Unknown StatusTreatmentLymphoblastic Leukemia, Acute1
3Unknown StatusTreatmentMalignant Lymphomas2
3WithdrawnTreatmentLeukemias1
4Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)4
4CompletedTreatmentAdult Acute Lymphocytic Leukemia4
4CompletedTreatmentLymphoma, Lymphoblastic1
4Enrolling by InvitationTreatmentChildhood Acute Promyelocytic Leukemia1
4RecruitingTreatmentAcute Lymphobkastic Leukemia1
4RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)2
4RecruitingTreatmentCrohn's Disease (CD)2
4RecruitingTreatmentInflammatory Bowel Diseases (IBD) / Pancreatitis1
4Unknown StatusTreatmentAdult Acute Lymphocytic Leukemia2
Not AvailableActive Not RecruitingTreatmentB-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
Not AvailableActive Not RecruitingTreatmentLeukemias1
Not AvailableCompletedNot AvailableImmune Thrombocytopenia1
Not AvailableCompletedNot AvailableInflammatory Bowel Diseases (IBD) / Psoriasis1
Not AvailableCompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
Not AvailableCompletedTreatmentAtaxia-Telangiectasia1
Not AvailableCompletedTreatmentB-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
Not AvailableCompletedTreatmentChildhood Acute Lymphoblastic Leukemia in Remission1
Not AvailableCompletedTreatmentLeukemias1
Not AvailableCompletedTreatmentLymphoma, Lymphoblastic1
Not AvailableCompletedTreatmentT-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
Not AvailableUnknown StatusNot AvailableAcute Lymphoblastic Leukaemias (ALL)1
Not AvailableUnknown StatusTreatmentLeukemias2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
TabletOral50 mg/1
TabletOral50 mg
SuspensionOral20 mg/mL
Prices
Unit descriptionCostUnit
Mercaptopurine powder33.97USD g
Purinethol 50 mg tablet6.09USD tablet
Mercaptopurine 50 mg tablet4.17USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)313 dec °CPhysProp
water solubility6.85E+004 mg/LYALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.01HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.735 mg/mLALOGPS
logP-0.13ALOGPS
logP-0.12ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)9.5ChemAxon
pKa (Strongest Basic)2.99ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area53.07 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity43.6 m3·mol-1ChemAxon
Polarizability14.04 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8854
Blood Brain Barrier+0.8946
Caco-2 permeable-0.6556
P-glycoprotein substrateNon-substrate0.7141
P-glycoprotein inhibitor INon-inhibitor0.9143
P-glycoprotein inhibitor IINon-inhibitor0.9848
Renal organic cation transporterNon-inhibitor0.8543
CYP450 2C9 substrateNon-substrate0.8607
CYP450 2D6 substrateNon-substrate0.8533
CYP450 3A4 substrateNon-substrate0.7949
CYP450 1A2 substrateInhibitor0.7555
CYP450 2C9 inhibitorNon-inhibitor0.6955
CYP450 2D6 inhibitorNon-inhibitor0.8224
CYP450 2C19 inhibitorNon-inhibitor0.7472
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6635
Ames testNon AMES toxic0.5076
CarcinogenicityNon-carcinogens0.9369
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.3684 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9857
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0udi-1900000000-80fade3542b1b7a4f542
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0udi-4900000000-ae3cab845511e09fd7d8
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-052f-9400000000-eb3a9e5b93f0954dda1f
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-066u-9300000000-e920208db376745577ae
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-014r-9100000000-9452425dda09b342a804
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-0900000000-fb1e1ed0d15536d940b5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9300000000-ae82c485895af50f18e0
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01ba-9700000000-70542617d846459d1edb
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00kb-9400000000-34922db319d482f338c7
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-7de65dacfd12ff92f5e4

Taxonomy

Description
This compound belongs to the class of organic compounds known as purinethiones. These are purines in which the purine moiety bears a thioketone.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
Purinethiones
Alternative Parents
Pyrimidinethiones / Imidazoles / Heteroaromatic compounds / Azacyclic compounds / Organosulfur compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
Substituents
Purinethione / Pyrimidinethione / Pyrimidine / Heteroaromatic compound / Imidazole / Azole / Azacycle / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aryl thiol (CHEBI:2208)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role...
Gene Name
HPRT1
Uniprot ID
P00492
Uniprot Name
Hypoxanthine-guanine phosphoribosyltransferase
Molecular Weight
24579.155 Da
References
  1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed:15354273]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Metal ion binding
Specific Function
Not Available
Gene Name
PPAT
Uniprot ID
Q06203
Uniprot Name
Amidophosphoribosyltransferase
Molecular Weight
57398.52 Da
References
  1. Sahasranaman S, Howard D, Roy S: Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. doi: 10.1007/s00228-008-0478-6. Epub 2008 May 28. [PubMed:18506437]
  2. Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP: ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1100-7. doi: 10.1093/nar/gkr777. Epub 2011 Sep 23. [PubMed:21948594]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Rna binding
Specific Function
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore pl...

Components:
References
  1. Sahasranaman S, Howard D, Roy S: Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. doi: 10.1007/s00228-008-0478-6. Epub 2008 May 28. [PubMed:18506437]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Thiopurine s-methyltransferase activity
Specific Function
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.
Gene Name
TPMT
Uniprot ID
P51580
Uniprot Name
Thiopurine S-methyltransferase
Molecular Weight
28180.09 Da
References
  1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed:15354273]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed:15354273]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
References
  1. Link [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Ohtsuki S, Asaba H, Takanaga H, Deguchi T, Hosoya K, Otagiri M, Terasaki T: Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain. J Neurochem. 2002 Oct;83(1):57-66. [PubMed:12358729]
  2. Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T: Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab. 2003 Apr;23(4):432-40. [PubMed:12679720]
  3. Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. [PubMed:15100168]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Chen ZS, Lee K, Kruh GD: Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. J Biol Chem. 2001 Sep 7;276(36):33747-54. Epub 2001 Jul 10. [PubMed:11447229]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Acts as a multispecific organic anion pump which can transport nucleotide analogs.
Gene Name
ABCC5
Uniprot ID
O15440
Uniprot Name
Multidrug resistance-associated protein 5
Molecular Weight
160658.8 Da
References
  1. Wijnholds J, Mol CA, van Deemter L, de Haas M, Scheffer GL, Baas F, Beijnen JH, Scheper RJ, Hatse S, De Clercq E, Balzarini J, Borst P: Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7476-81. [PubMed:10840050]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Purine nucleoside transmembrane transporter activity
Specific Function
Sodium-dependent and purine-selective transporter. Exhibits the transport characteristics of the nucleoside transport system cif or N1 subtype (N1/cif) (selective for purine nucleosides and uridine...
Gene Name
SLC28A2
Uniprot ID
O43868
Uniprot Name
Sodium/nucleoside cotransporter 2
Molecular Weight
71925.565 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function
Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtyp...
Gene Name
SLC28A3
Uniprot ID
Q9HAS3
Uniprot Name
Solute carrier family 28 member 3
Molecular Weight
76929.61 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, ...
Gene Name
SLC29A2
Uniprot ID
Q14542
Uniprot Name
Equilibrative nucleoside transporter 2
Molecular Weight
50112.335 Da
References
  1. Link [Link]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2017 19:27