Identification

Name
Tioguanine
Accession Number
DB00352  (APRD00290)
Type
Small Molecule
Groups
Approved
Description

An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [PubChem]

Structure
Thumb
Synonyms
  • 2-Amino 6mp
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-amino-1,9-Dihydropurine-6-thione
  • 2-amino-1H-purine-6(7H)-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-merkaptopurin
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-aminopurine-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6-Thioguanine
  • TG
  • ThG
  • Thioguanine
  • Tioguanin
  • Tioguanina
  • Tioguanine
  • Tioguaninum
External IDs
6-TG / NSC 752 / NSC-752 / NSC-76504 / Wellcome U 3 B
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LanvisTablet40 mgOralAspen Pharmacare Canada Inc.1974-12-31Not applicableCanada
TabloidTablet40 mg/1OralAspen Global Inc.2013-03-12Not applicableUs
International/Other Brands
Tioguanina (Induquimica) / Tioguanine (IFET)
Categories
UNII
WIX31ZPX66
CAS number
154-42-7
Weight
Average: 167.192
Monoisotopic: 167.026565875
Chemical Formula
C5H5N5S
InChI Key
WYWHKKSPHMUBEB-UHFFFAOYSA-N
InChI
InChI=1S/C5H5N5S/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11)
IUPAC Name
2-amino-6,7-dihydro-3H-purine-6-thione
SMILES
NC1=NC(=S)C2=C(N1)N=CN2

Pharmacology

Indication

For remission induction and remission consolidation treatment of acute nonlymphocytic leukemias.

Structured Indications
Pharmacodynamics

Thioguanine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Thioguanine was first synthesized and entered into clinical trial more than 30 years ago. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Thioguanine is cross-resistant with mercaptopurine. Cytotoxicity is cell cycle phase-specific (S-phase).

Mechanism of action

Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses. TGMP interferes with the synthesis of guanine nucleotides by its inhibition of purine biosynthesis by pseudofeedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway of purine ribonucleotide synthesis. TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and some studies have shown that incorporation of such false bases contributes to the cytotoxicity of thioguanine. Its tumor inhibitory properties may be due to one or more of its effects on feedback inhibition of de novo purine synthesis; inhibition of purine nucleotide interconversions; or incorporation into the DNA and RNA. The overall result of its action is a sequential blockade of the utilization and synthesis of the purine nucleotides.

TargetActionsOrganism
ADNA
intercalation
Human
Absorption

Absorption of an oral dose is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%)

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic. First converted to 6-thioguanilyic acid (TGMP). TGMP is further converted to the di- and tri-phosphates, thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP) by the same enzymes that metabolize guanine nucleotides.

Route of elimination
Not Available
Half life

When the compound was given in singles doses of 65 to 300 mg/m^2, the median plasma half-disappearance time was 80 minutes (range 25-240 minutes)

Clearance
Not Available
Toxicity

Oral, mouse: LD50 = 160 mg/kg. Symptoms of overdose include nausea, vomiting, malaise, hypotension, and diaphoresis.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Thioguanine Metabolism PathwayDrug metabolism
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 StudiedThe presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine.Details
Thiopurine S-methyltransferaseTPMT*3A(A;A) / (A;G)A AlleleADR Directly StudiedThe presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine.Details
Thiopurine S-methyltransferaseTPMT*3C(G;G) / (A;G)G AlleleADR Directly StudiedThe presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine.Details
Thiopurine S-methyltransferaseTPMT*4A(A;A) / (A;G)G > AADR Directly StudiedThe presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine.Details
Thiopurine S-methyltransferaseTPMT*3BNot Availablec.460G>AADR InferredSevere myelosuppression.Details

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Tioguanine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Tioguanine.Experimental
BalsalazideThe metabolism of Tioguanine can be decreased when combined with Balsalazide.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Tioguanine.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Tioguanine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Tioguanine.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Tioguanine.Approved
ClozapineThe risk or severity of adverse effects can be increased when Tioguanine is combined with Clozapine.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Tioguanine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Tioguanine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Tioguanine.Experimental
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Tioguanine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Tioguanine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Tioguanine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Tioguanine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Tioguanine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Tioguanine.Approved, Investigational
FingolimodTioguanine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Tioguanine.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Tioguanine.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Tioguanine.Experimental
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Tioguanine.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Tioguanine.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Tioguanine.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Tioguanine.Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Tioguanine.Experimental
LeflunomideThe risk or severity of adverse effects can be increased when Tioguanine is combined with Leflunomide.Approved, Investigational
MesalazineThe metabolism of Tioguanine can be decreased when combined with Mesalazine.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Tioguanine.Investigational, Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Tioguanine.Experimental
NatalizumabThe risk or severity of adverse effects can be increased when Tioguanine is combined with Natalizumab.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Tioguanine.Experimental, Investigational
OlsalazineThe metabolism of Tioguanine can be decreased when combined with Olsalazine.Approved
OuabainOuabain may decrease the cardiotoxic activities of Tioguanine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Tioguanine.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Tioguanine.Experimental
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Tioguanine.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Tioguanine.Experimental
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Tioguanine 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 Tioguanine.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Tioguanine.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Tioguanine.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Tioguanine.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Tioguanine.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Tioguanine.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Tioguanine.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Tioguanine.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Tioguanine.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Tioguanine.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Tioguanine.Investigational
TofacitinibTioguanine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Tioguanine.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Tioguanine.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Tioguanine.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14496
KEGG Drug
D06109
KEGG Compound
C07648
PubChem Compound
2723601
PubChem Substance
46508170
ChemSpider
2005804
BindingDB
50200099
ChEBI
9555
ChEMBL
CHEMBL727
Therapeutic Targets Database
DAP000194
PharmGKB
PA451663
HET
DX4
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Thioguanine
ATC Codes
L01BB03 — Tioguanine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3jqa / 3rkf / 4m5m / 4xoy / 4xp3
FDA label
Download (174 KB)
MSDS
Download (30.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentLeukemias1
1TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Recurrent Pediatric ALL / Refractory Pediatric ALL / Relapsed Pediatric ALL1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
1, 2WithdrawnTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Active Not RecruitingTreatmentLeukaemia, Lymphoblastic / Lymphoma, Lymphoblastic1
2Active Not RecruitingTreatmentLeukemias1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL)1
2CompletedTreatmentAnaplastic Glioma of Brain / Brain Cancer / Glioblastoma Multiforme1
2CompletedTreatmentHodgkins Disease (HD)1
2CompletedTreatmentLangerhans Cell Histiocytosis (LCH)1
2CompletedTreatmentLeukemias3
2CompletedTreatmentLeukemias / Neutropenias / Thrombocytopenias1
2CompletedTreatmentMalignant Lymphomas1
2RecruitingTreatmentAcute Leukemias of Ambiguous Lineage / Childhood B Acute Lymphoblastic Leukemia / KMT2A Gene Rearrangement / Mixed Phenotype Acute Leukemia (MPAL)1
2RecruitingTreatmentB-cell Acute Lymphoblastic Leukemia1
2RecruitingTreatmentLeukaemia, Lymphoblastic1
2TerminatedTreatmentLeukemias / Lymphoma, Lymphoblastic / Malignant Lymphomas / Precursor-B Acute Lymphoblastic Leukemia1
2TerminatedTreatmentLymphoma, Lymphoblastic1
2Unknown StatusTreatmentLeukemias1
2, 3RecruitingTreatmentLeukemias1
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 RecruitingTreatmentB-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentChildhood Acute Basophilic Leukemia / Childhood Acute Eosinophilic Leukemia / Childhood Acute Erythroleukemia (M6) / Childhood Acute Megakaryocytic Leukemia (M7) / Childhood Acute Minimally Differentiated Myeloid Leukemia (M0) / Childhood Acute Monoblastic Leukemia (M5a) / Childhood Acute Monocytic Leukemia (M5b) / Childhood Acute Myeloblastic Leukemia With Maturation (M2) / Childhood Acute Myeloblastic Leukemia Without Maturation (M1) / Childhood Acute Myelomonocytic Leukemia (M4) / Childhood Myelodysplastic Syndromes / De Novo Myelodysplastic Syndromes / Secondary Acute Myeloid Leukemia / Secondary Myelodysplastic Syndromes / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3Active Not RecruitingTreatmentLeukemias1
3Active Not RecruitingTreatmentMalignant Lymphomas1
3CompletedTreatmentChildhood Acute Erythroleukemia (M6) / Childhood Acute Megakaryocytic Leukemia (M7) / Childhood Acute Monoblastic Leukemia (M5a) / Childhood Acute Monocytic Leukemia (M5b) / Childhood Acute Myeloblastic Leukemia With Maturation (M2) / Childhood Acute Myeloblastic Leukemia Without Maturation (M1) / Childhood Acute Myelomonocytic Leukemia (M4) / Childhood Myelodysplastic Syndromes / Chronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndromes / Refractory Anemia / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation / Refractory Anemia With Ringed Sideroblasts / Secondary Myelodysplastic Syndromes / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
3CompletedTreatmentLeukemias11
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms2
3CompletedTreatmentNeoplasms, Brain / Tumors, Central Nervous System1
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
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
3RecruitingTreatmentChildhood Acute Myeloid Leukemia / Childhood Myelodysplastic Syndrome / Cytopenias / Down Syndrome (DS) / Myeloid Leukemia Associated With Down Syndrome / Myeloproliferative Neoplasms1
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
3TerminatedTreatmentMalignant Lymphomas1
3Unknown StatusTreatmentLeukemias3
3Unknown StatusTreatmentLeukemias / Malignant Lymphomas1
3Unknown StatusTreatmentLeukemias / Neutropenias1
3Unknown StatusTreatmentMalignant Lymphomas1
4CompletedTreatmentAdult Acute Lymphocytic Leukemia3
4CompletedTreatmentLymphoma, Lymphoblastic1
4RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4Unknown StatusTreatmentAdult Acute Lymphocytic Leukemia1
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 AvailableCompletedTreatmentB-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
Not AvailableCompletedTreatmentT-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
Not AvailableUnknown StatusTreatmentLeukemias2

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
Packagers
Dosage forms
FormRouteStrength
TabletOral40 mg
TabletOral40 mg/1
Prices
Unit descriptionCostUnit
Thioguanine tabloid 40 mg tablet9.88USD each
Tabloid tablet9.44USD 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)>360 °CPhysProp
water solubility36.3 mg/mLNot Available
logP-0.07HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.834 mg/mLALOGPS
logP-0.36ALOGPS
logP-0.35ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)10.53ChemAxon
pKa (Strongest Basic)3.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area79.09 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity46.89 m3·mol-1ChemAxon
Polarizability15.65 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8857
Blood Brain Barrier+0.8663
Caco-2 permeable-0.5722
P-glycoprotein substrateNon-substrate0.7403
P-glycoprotein inhibitor INon-inhibitor0.9168
P-glycoprotein inhibitor IINon-inhibitor0.9745
Renal organic cation transporterNon-inhibitor0.8499
CYP450 2C9 substrateNon-substrate0.8862
CYP450 2D6 substrateNon-substrate0.8332
CYP450 3A4 substrateNon-substrate0.7974
CYP450 1A2 substrateInhibitor0.7904
CYP450 2C9 inhibitorNon-inhibitor0.6575
CYP450 2D6 inhibitorNon-inhibitor0.8881
CYP450 2C19 inhibitorInhibitor0.5517
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8537
Ames testNon AMES toxic0.7731
CarcinogenicityNon-carcinogens0.9255
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.1583 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9743
hERG inhibition (predictor II)Non-inhibitor0.8918
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

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 / Aminopyrimidines and derivatives / Imidazoles / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organosulfur compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Purinethione / Aminopyrimidine / Pyrimidinethione / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Azacycle / Organopnictogen compound / Primary amine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
2-aminopurines (CHEBI:9555)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Schwartz EL, Ishiguro K, Sartorelli AC: Induction of leukemia cell differentiation by chemotherapeutic agents. Adv Enzyme Regul. 1983;21:3-20. [PubMed:6400065]
  2. Riscoe MK, Brouns MC, Fitchen JH: Purine metabolism as a target for leukemia chemotherapy. Blood Rev. 1989 Sep;3(3):162-73. [PubMed:2676034]
  3. 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]
  4. Coulthard S, Hogarth L: The thiopurines: an update. Invest New Drugs. 2005 Dec;23(6):523-32. [PubMed:16267626]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Shivashankar K, Subbayya IN, Balaram H: Development of a bacterial screen for novel hypoxanthine-guanine phosphoribosyltransferase substrates. J Mol Microbiol Biotechnol. 2001 Oct;3(4):557-62. [PubMed:11545274]
  2. Horikawa K, Kawaguchi T, Ishihara S, Nagakura S, Hidaka M, Kagimoto T, Mitsuya H, Nakakuma H: Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2002 Jan 1;99(1):24-9. [PubMed:11756148]
  3. Fuscoe JC, Zimmerman LJ, Fekete A, Setzer RW, Rossiter BJ: Analysis of X-ray-induced HPRT mutations in CHO cells: insertion and deletions. Mutat Res. 1992 Oct;269(2):171-83. [PubMed:1383700]
  4. Elgemeie GH: Thioguanine, mercaptopurine: their analogs and nucleosides as antimetabolites. Curr Pharm Des. 2003;9(31):2627-42. [PubMed:14529546]
  5. Suzuki M, Tsuruoka C, Kanai T, Kato T, Yatagai F, Watanabe M: Qualitative and quantitative difference in mutation induction between carbon- and neon-ion beams in normal human cells. Biol Sci Space. 2003 Dec;17(4):302-6. [PubMed:15136753]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. [PubMed:14643890]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33