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Thioguanine

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Also known as LanvisNSC-752NSC-76504TabloidThioguanine anhydrousThioguanine hemihydrateanhydrousTioguaninaTioguanineTioguanine hemihydrateThioquanineSID26748270SID57260104SID538243SID144204586SID144206735SID57264437SID144210595SID170464908

Summary

Thioguanine (CHEMBL727) is an approved small-molecule antineoplastic agent (ATC L01BB03) targeting IMPDH1 and IMPDH2; indicated across 28 conditions including neoplasm and acute lymphoblastic leukemia; with CIViC clinical evidence for 29 variant-indication associations (e.g. NUDT15 Inactivating Mutation in childhood acute lymphocytic leukemia).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01BB03
  • Targets: 2 (IMPDH1, IMPDH2)
  • Indications: 28 conditions
  • Clinical trials: 85
  • Precision-oncology evidence (CIViC): 29 variant–indication associations
  • Chemistry: 167.19 Da · C5H5N5S

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL727
NameThioguanine
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID2723601
ChEBICHEBI:9555
ATCL01BB03
Molecular formulaC5H5N5S
Molecular weight167.19
InChIKeyWYWHKKSPHMUBEB-UHFFFAOYSA-N

SMILES: C1=NC2=C(N1)C(=S)N=C(N2)N

IUPAC name: 2-amino-3,7-dihydropurine-6-thione

ChEBI definition: A 2-aminopurine that is the 6-thiono derivative of 2-amino-1,9-dihydro-6H-purine. Incorporates into DNA and inhibits synthesis. Used in the treatment of leukaemia.

Pharmacological roles (ChEBI): antineoplastic agent, anticoronaviral agent.

Other ChEBI roles (chemical / environmental): antimetabolite.

Also known as: Lanvis, NSC-752, NSC-76504, Tabloid, Thioguanine, Thioguanine anhydrous, Thioguanine hemihydrate, anhydrous, Tioguanina, Tioguanine, Tioguanine hemihydrate, thioguanine

Patent coverage: 71,510 distinct patent families (294,612 SureChEMBL compound mentions), from 5 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
IMPDH1inosine monophosphate dehydrogenase 1Inhibition8.8%P20839
IMPDH2inosine monophosphate dehydrogenase 2Inhibition48.5%P12268

Broader ChEMBL bioactivity targets: 16 (assay-derived). Sample: Ubiquitin carboxyl-terminal hydrolase 2, Survival motor neuron protein, Fructose-bisphosphate aldolase, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], Xanthine dehydrogenase/oxidase, Prostaglandin G/H synthase 1, Paired box protein Pax-8, Adenosine receptor A3, 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase, Tyrosinase.

Bioactivity

ChEMBL activities: 14 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
P0DTD17IC50100nMCHEMBL_ACT_24819084
P0DTD16.3IC50500nMCHEMBL_ACT_24819082
PTGS16.22IC50601nMCHEMBL_ACT_7795724
PTGS16.09AC50810nMCHEMBL_ACT_25205239
P0DTD16IC501000nMCHEMBL_ACT_24819083
HBB5.95Potency1122nMCHEMBL_ACT_4107382
PAX85.93AC501180nMCHEMBL_ACT_13091821
PTGS15.88AC501320nMCHEMBL_ACT_25206172
A8B2U25.5Potency3155nMCHEMBL_ACT_4606932
TP535.4Potency3981nMCHEMBL_ACT_4830026
TP535.4Potency3981nMCHEMBL_ACT_4866561
HBB5.3Potency5012nMCHEMBL_ACT_3765572
MAPK35.26IC505516nMCHEMBL_ACT_7797841
SMN15.15Potency7080nMCHEMBL_ACT_3862668

Target pathways

Aggregated over 2 target gene(s): IMPDH1, IMPDH2.

Top Reactome pathways

14 total, by targets touching each:

PathwayTargetsGenes
Metabolism2IMPDH1, IMPDH2
Metabolism of nucleotides2IMPDH1, IMPDH2
Disease2IMPDH1, IMPDH2
Innate Immune System2IMPDH1, IMPDH2
Immune System2IMPDH1, IMPDH2
Infectious disease2IMPDH1, IMPDH2
Neutrophil degranulation2IMPDH1, IMPDH2
Purine ribonucleoside monophosphate biosynthesis2IMPDH1, IMPDH2
Nucleotide biosynthesis2IMPDH1, IMPDH2
Potential therapeutics for SARS2IMPDH1, IMPDH2
SARS-CoV Infections2IMPDH1, IMPDH2
Drug ADME2IMPDH1, IMPDH2
Azathioprine ADME2IMPDH1, IMPDH2
Viral Infection Pathways2IMPDH1, IMPDH2

Dominant GO biological processes

GO termTargets
GMP biosynthetic process2
GTP biosynthetic process2
lymphocyte proliferation2
‘de novo’ XMP biosynthetic process2
purine nucleotide biosynthetic process2
circadian rhythm1
cellular response to interleukin-41

Indications & clinical

Indications

28 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
acute lymphoblastic leukemia3MONDO:0004967EFO:0000220
myelodysplastic syndrome3MONDO:0018881EFO:0000198
acute myeloid leukemia3MONDO:0018874EFO:0000222
leukemia3MONDO:0005059EFO:0000565
lymphoma3MONDO:0005062EFO:0000574
T-cell acute lymphoblastic leukemia3MONDO:0004963EFO:0000209
acute erythroid leukemia3MONDO:0017858EFO:0000218
acute monocytic leukemia3MONDO:0007896EFO:0000221
acute myelomonocytic leukemia M43MONDO:0018871EFO:0000223
acute megakaryoblastic leukemia3MONDO:0018872EFO:0003025
acute myeloblastic leukemia without maturation3MONDO:0005224EFO:0003027
myelodysplastic syndrome with single lineage dysplasia3MONDO:0005272EFO:0003802
myelodysplastic syndrome with excess blasts3MONDO:0019454EFO:0003811
brain neoplasm3MONDO:0021211EFO:0003833
chronic myelomonocytic leukemia3MONDO:0020311EFO:1001779
brain cancer3MONDO:0001657MONDO:0001657
acute basophilic leukemia3MONDO:0019458EFO:0003029
lymphoid leukemia3MONDO:0005402EFO:0004289
central nervous system neoplasm3MONDO:0006130EFO:1000158
Hodgkins lymphoma2MONDO:0004952EFO:0000183
glioblastoma2MONDO:0018177EFO:0000519
Langerhans cell histiocytosis2MONDO:0018310EFO:1000318
non-Hodgkin lymphoma1MONDO:0018908EFO:0005952

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 85.

Phase distribution

PhaseTrials
PHASE342
PHASE224
PHASE46
Not specified4
PHASE2/PHASE33
PHASE1/PHASE23
PHASE13

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00198991PHASE4COMPLETEDGerman Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (07/2003)
NCT00199004PHASE4COMPLETEDTrial for Treatment of Adult Patients With Standard Risk Acute Lymphoblastic Leukemia With Chemotherapy and Rituximab
NCT00199017PHASE4COMPLETEDGerman Multicenter Trial for the Treatment of Newly Diagnosed T-lymphoblastic Lymphoma in Adults
NCT00199056PHASE4COMPLETEDGerman Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (06/99)
NCT00199069PHASE4COMPLETEDGerman Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (05/93)
NCT02894645PHASE4UNKNOWNMalaysia-Singapore Acute Lymphoblastic Leukemia 2010 Study
NCT02101853PHASE3ACTIVE_NOT_RECRUITINGBlinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
NCT02112916PHASE3ACTIVE_NOT_RECRUITINGCombination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma
NCT02521493PHASE3ACTIVE_NOT_RECRUITINGResponse-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
NCT03007147PHASE3ACTIVE_NOT_RECRUITINGImatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
NCT03117751PHASE2/PHASE3ACTIVE_NOT_RECRUITINGTotal Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma
NCT03150693PHASE3RECRUITINGInotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia
NCT03914625PHASE3ACTIVE_NOT_RECRUITINGA Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
NCT03959085PHASE3RECRUITINGInotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
NCT04043494PHASE3RECRUITINGInternational Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma
NCT07072585PHASE2/PHASE3NOT_YET_RECRUITINGTesting the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL)
NCT00002514PHASE3COMPLETEDStem Cell Transplantation Compared With Standard Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia in First Remission
NCT00002517PHASE3COMPLETEDCombination Chemotherapy in Treating Children With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT00002658PHASE3UNKNOWNCombination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002701PHASE3UNKNOWNCombination Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Promyelocytic Leukemia
NCT00002744PHASE3COMPLETEDCombination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia
NCT00002798PHASE3COMPLETEDCombination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
NCT00002812PHASE3COMPLETEDCombination Chemotherapy in Treating Children With Acute Lymphocytic Leukemia
NCT00002816PHASE3COMPLETEDCombination Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia
NCT00002944PHASE3COMPLETEDCombination Chemotherapy in Treating Children With Progressive Brain Tumors
NCT00003423PHASE3UNKNOWNCombination Chemotherapy in Treating Children With Non-Hodgkin’s Lymphoma
NCT00003437PHASE3UNKNOWNHormone Therapy Plus Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia
NCT00003593PHASE3COMPLETEDChemotherapy in Treating Children With Down Syndrome and Myeloproliferative Disorder, Acute Myelogenous Leukemia, or Myelodysplastic Syndrome
NCT00003728PHASE3UNKNOWNCombination Chemotherapy Plus Steroid Therapy in Treating Children With Acute Lymphoblastic Leukemia or Lymphoblastic Non-Hodgkin’s Lymphoma
NCT00004228PHASE3COMPLETEDCombination Chemotx in Treating Children or Adolescents With Newly Diagnosed Stg III or Stg IV Lymphoblastic Lymphoma
NCT00005585PHASE3COMPLETEDCombination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia
NCT00005596PHASE3COMPLETEDCombination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia
NCT00005603PHASE3COMPLETEDCombination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia
NCT00005823PHASE3COMPLETEDIntensive Compared With Nonintensive Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT00005945PHASE3COMPLETEDComparison of Different Combination Chemotherapy Regimens in Treating Children With Acute Lymphoblastic Leukemia
NCT00075725PHASE3COMPLETEDDexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia
NCT00103285PHASE3COMPLETEDCombination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
NCT00186966PHASE3COMPLETEDTreatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
NCT00266136PHASE3COMPLETEDBiology and Treatment Strategy of AML in Its Subgroups: Multicenter Randomized Trial by the German Acute Myeloid Leukemia Cooperative Group (AMLCG)
NCT00275106PHASE3TERMINATEDPrednisolone or Dexamethasone Combined With Chemotherapy in Treating Young Patients With Newly Diagnosed Lymphoblastic Lymphoma

Clinical evidence (CIViC)

Variant × indication × effect (29 predictive associations from 29 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
NUDT15 Inactivating MutationChildhood Acute Lymphocytic LeukemiaAdverse ResponseAzathioprine + Mercaptopurine + ThioguanineCIViC BEID7794
NT5C2 R367QChildhood Acute Lymphocytic LeukemiaResistanceMercaptopurine + ThioguanineCIViC CEID7812
NT5C2 D407AT-cell Acute Lymphoblastic LeukemiaResistanceThioguanine + MercaptopurineCIViC DEID632
NT5C2 K359QT-cell Acute Lymphoblastic LeukemiaResistanceMercaptopurine + ThioguanineCIViC DEID631
NT5C2 R238WChildhood Acute Lymphocytic LeukemiaResistanceMercaptopurine + ThioguanineCIViC DEID7813
NT5C2 R238WB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID8077
NT5C2 R367QT-cell Acute Lymphoblastic LeukemiaResistanceMercaptopurine + ThioguanineCIViC DEID630
NT5C2 R367QChildhood Acute Lymphocytic LeukemiaResistanceThioguanine + MercaptopurineCIViC DEID7862
NT5C2 S445FChildhood Acute Lymphocytic LeukemiaResistanceMercaptopurine + ThioguanineCIViC DEID7814
PRPS1 A190TB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7909
PRPS1 A190VB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7908
PRPS1 A87TB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7919
PRPS1 C77SB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7916
PRPS1 D139GB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7915
PRPS1 D183EB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7900
PRPS1 D183HB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7897
PRPS1 G174EB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7902
PRPS1 I72VB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7917
PRPS1 K176NB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7901
PRPS1 L191FB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7899
PRPS1 M115TB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7920
PRPS1 N114DB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7904
PRPS1 N144SB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7903
PRPS1 S103IB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7905
PRPS1 S103NB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7906
PRPS1 S103TB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7907
PRPS1 T303SB-lymphoblastic Leukemia/lymphomaResistanceMercaptopurine + ThioguanineCIViC DEID7898
PRPS1 V53AB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7918
PRPS1 Y311CB-lymphoblastic Leukemia/lymphomaResistanceThioguanine + MercaptopurineCIViC DEID7914

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (3) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

GuidelineSourceGene(s)DosingRecommendation
Annotation of DPWG Guideline for thioguanine and TPMTDPWGTPMTyesyes
Annotation of CPIC Guideline for thioguanine and NUDT15, TPMTCPICNUDT15;TPMTyesyes
Annotation of DPWG Guideline for thioguanine and NUDT15DPWGNUDT15yesyes

PharmGKB also curates 15 clinical and 45 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

23 molecules share ≥1 primary target. Top 23 by shared-target count:

MoleculeSourceStatusShared targets
MYCOPHENOLIC ACIDChEMBL + PubChemPhase 4 (approved)IMPDH1, IMPDH2
MERIMEPODIBChEMBLPhase 2IMPDH1, IMPDH2
AdenosinePubChemApprovedIMPDH1
AfatinibPubChemApprovedIMPDH2
BinimetinibPubChemApprovedIMPDH2
CobimetinibPubChemApprovedIMPDH2
CrizotinibPubChemApprovedIMPDH2
dacomitinibPubChemApprovedIMPDH2
ErlotinibPubChemApprovedIMPDH2
FedratinibPubChemApprovedIMPDH2
FostamatinibPubChemApprovedIMPDH2
GefitinibPubChemApprovedIMPDH2
IdelalisibPubChemApprovedIMPDH2
LapatinibPubChemApprovedIMPDH2
NadidePubChemApprovedIMPDH1
PazopanibPubChemApprovedIMPDH2
regorafenibPubChemApprovedIMPDH2
RibavirinPubChemApprovedIMPDH1
SelumetinibPubChemApprovedIMPDH2
SorafenibPubChemApprovedIMPDH2
TirbanibulinPubChemApprovedIMPDH2
TrametinibPubChemApprovedIMPDH2
VorinostatPubChemApprovedIMPDH1

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot