Drug Information

Drug (ID: DG00040) and It's Reported Resistant Information
Name
Thioguanine
Synonyms
6-thioguanine; Lanvis; THG; Tabloid; ThioguaninGSK; Tioguanin; Tioguanina; Tioguanine; Tioguaninum; Glaxo Wellcome Brand of Thioguanine; Glaxo Wellcome Brand of Tioguanine; GlaxoSmithKline Brand of Thioguanine; GlaxoSmithKline Brand of Tioguanine; Thioguanin GSK; Thioguanine Hemihydrate; Thioguanine Monosodium Salt; Thioguanine Tabloid; Tioguanina Wellcome; Tioguanine GlaxoSmithKline Brand; Wellcome Brand of Thioguanine; BW 5071; DX4; LT00455187; Wellcome U3B; Lanvis (TN); Thioguanin-GSK; Thioguanine [USAN:BAN]; Tioguanina[INN-Spanish]; Tioguanine (INN); Tioguaninum [INN-Latin]; Purine antimetabolite: antimetabolite: inhibits nucleic acid replication; Guanine, thio-(VAN); 2 Amino 6 Purinethiol; 2-Amino 6MP; 2-Amino-1,7-dihydro-6H-purin-6-thion; 2-Amino-1,7-dihydro-6H-purin-6-thion [Czech]; 2-Amino-1,7-dihydro-6H-purine-6-thione; 2-Amino-6-MP; 2-Amino-6-mercaptopurine; 2-Amino-6-merkaptopurin; 2-Amino-6-merkaptopurin [Czech]; 2-Amino-6-purinethiol; 2-Amino-9H-purine-6-thiol; 2-Aminopurin-6-thiol; 2-Aminopurin-6-thiol [Czech]; 2-Aminopurine-6(1H)-thione; 2-Aminopurine-6-thiol; 2-Thioguanine; 2-amino-3,7-dihydropurine-6-thione; 6 Thioguanine; 6-Mercapto-2-aminopurine; 6-Mercaptoguanine; 6-TG; 6-Thioguanine; 6-Thioguanine (6-TG); 6-Thioguanine, Thioguanine; Thioguanine (Guanine analog)
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Indication
In total 1 Indication(s)
Acute myeloid leukaemia [ICD-11: 2A60]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
Acute lymphocytic leukemia [ICD-11: 2B33]
[1]
Acute myeloid leukemia [ICD-11: 2A60]
[2], [3]
Target Inosine-5'-monophosphate dehydrogenase (IMPDH) NOUNIPROTAC [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C5H5N5S
IsoSMILES
C1=NC2=C(N1)C(=S)N=C(N2)N
InChI
1S/C5H5N5S/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11)
InChIKey
WYWHKKSPHMUBEB-UHFFFAOYSA-N
PubChem CID
2723601
ChEBI ID
CHEBI:9555
TTD Drug ID
D02ZXM
VARIDT ID
DR00510
INTEDE ID
DR1597
DrugBank ID
DB00352
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  DISM: Drug Inactivation by Structure Modification
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
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Acute myeloid leukemia [ICD-11: 2A60]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Cytosolic purine 5'-nucleotidase (NT5C2) [2], [3]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R238W (c.c712t)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 5OPP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.84  Å
PDB: 5L4Z
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.41
TM score: 0.99758
Amino acid change:
R238W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Exome sequencing assay; Transcriptome sequencing assay; Whole genome sequencing assay; Sanger Sequencing assay
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Several of these alterations are known to induce a more stem cell-like state (eg, IkZF1) or confer resistance directly to specific chemotherapy agents such as CREBBP and glucocorticoids and mutations in the 5-nucleotidase gene NT5C2 and nucleoside a.logs. Many relapse-acquired lesions are enriched in specific pathways, including B-cell development (IkZF1), tumor suppression (TP53),34 Ras signaling, chromatin modification (CREBBP, SETD2),17 and drug metabolism (NT5C2).
References
Ref 1 The clonal evolution of leukemic stem cells in T-cell acute lymphoblastic leukemia. Curr Opin Hematol. 2014 Jul;21(4):320-5. doi: 10.1097/MOH.0000000000000058.
Ref 2 Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat Genet. 2013 Mar;45(3):290-4. doi: 10.1038/ng.2558. Epub 2013 Feb 3.
Ref 3 The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):174-80. doi: 10.1182/asheducation-2014.1.174. Epub 2014 Nov 18.

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