General Information of Drug Combination (ID: DC2BJHM)

Drug Combination Name
Thioguanine Pomalidomide
Indication
Disease Entry Status REF
Clear cell renal cell carcinoma Investigative [1]
Component Drugs Thioguanine   DM7NKEV Pomalidomide   DMTGBAX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: CAKI-1
Zero Interaction Potency (ZIP) Score: 8.37
Bliss Independence Score: 14.45
Loewe Additivity Score: 1.88
LHighest Single Agent (HSA) Score: 14.56

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Thioguanine
Disease Entry ICD 11 Status REF
Acute lymphocytic leukaemia 2B33.3 Approved [2]
Acute myelogenous leukaemia 2A41 Approved [3]
Acute myeloid leukaemia 2A60 Approved [4]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [5]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [5]
Thioguanine Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MERS-CoV papain-like proteinase (PL-PRO) TTYJOLE R1AB_CVEMC (854-2740) Inhibitor [5]
Inosine-5'-monophosphate dehydrogenase (IMPDH) TTCAQMW NOUNIPROTAC Intercalator [8]
SARS-CoV papain-like proteinase (PL-PRO) TTRGHB2 R1AB_CVHSA (819-2740) Inhibitor [5]
------------------------------------------------------------------------------------
Thioguanine Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [10]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3) DT4YL5R S28A3_HUMAN Substrate [11]
------------------------------------------------------------------------------------
Thioguanine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [12]
Hypoxanthine phosphoribosyltransferase (HPRT1) DEVXTP5 HPRT_HUMAN Metabolism [13]
------------------------------------------------------------------------------------
Thioguanine Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Thiopurine S-methyltransferase (TPMT) OTFOX70W TPMT_HUMAN Increases ADR [14]
Hypoxanthine-guanine phosphoribosyltransferase (HPRT1) OTOEEEXG HPRT_HUMAN Decreases Response To Substance [15]
Thiopurine S-methyltransferase (TPMT) OTFOX70W TPMT_HUMAN Increases ADR [16]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) OTPG0K7E IMDH2_HUMAN Increases Expression [17]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [18]
Dystrophin (DMD) OTD21T5J DMD_HUMAN Increases Splicing [19]
Occludin (OCLN) OTSUTVWL OCLN_HUMAN Decreases Activity [20]
DNA mismatch repair protein Msh2 (MSH2) OT10H1AB MSH2_HUMAN Increases Response To Substance [21]
ATP-binding cassette sub-family C member 5 (ABCC5) OT34G4US MRP5_HUMAN Decreases Response To Substance [22]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Response To Substance [18]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [23]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 DOT(s)
Indication(s) of Pomalidomide
Disease Entry ICD 11 Status REF
Plasma cell myeloma 2A83.1 Approved [6]
Systemic sclerosis 4A42 Approved [7]
Pomalidomide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiogenesis/myeloma cell growth (AMCG) TTDIBYJ NOUNIPROTAC Modulator [24]
------------------------------------------------------------------------------------
Pomalidomide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [25]
------------------------------------------------------------------------------------
Pomalidomide Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [26]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [27]
------------------------------------------------------------------------------------
Pomalidomide Interacts with 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [28]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Secretion [29]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Secretion [29]
Granulocyte colony-stimulating factor (CSF3) OT9GC6TP CSF3_HUMAN Increases Secretion [29]
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Decreases Expression [30]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [29]
Erythroid transcription factor (GATA1) OTX1R7O1 GATA1_HUMAN Decreases Expression [29]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Decreases Expression [29]
Transcription factor PU.1 (SPI1) OTVCA1D0 SPI1_HUMAN Increases Expression [29]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [29]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Affects Expression [30]
Endothelial transcription factor GATA-2 (GATA2) OTBP2QQ2 GATA2_HUMAN Decreases Expression [29]
Rhombotin-2 (LMO2) OTCC370G RBTN2_HUMAN Decreases Expression [29]
Interleukin-13 (IL13) OTI4YS3Y IL13_HUMAN Decreases Secretion [29]
DNA-binding protein inhibitor ID-1 (ID1) OTKGNZN5 ID1_HUMAN Increases Expression [29]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Increases Expression [29]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [29]
DNA-binding protein inhibitor ID-2 (ID2) OT0U1D53 ID2_HUMAN Increases Expression [29]
Krueppel-like factor 1 (KLF1) OT1FK08U KLF1_HUMAN Decreases Expression [29]
CCAAT/enhancer-binding protein epsilon (CEBPE) OTKZA25M CEBPE_HUMAN Increases Expression [29]
Transcription factor NF-E2 45 kDa subunit (NFE2) OTLM94BI NFE2_HUMAN Decreases Expression [29]
Zinc finger protein Gfi-1b (GFI1B) OTRDW8YO GFI1B_HUMAN Decreases Expression [29]
Zinc finger protein Gfi-1 (GFI1) OT9HB9H8 GFI1_HUMAN Increases Expression [29]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [31]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Oxidation [28]
Cytochrome P450 2J2 (CYP2J2) OTJBTEH8 CP2J2_HUMAN Increases Oxidation [28]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [32]
------------------------------------------------------------------------------------
⏷ Show the Full List of 27 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Glioma DC9MLLQ SF-295 Investigative [1]
Renal cell carcinoma DCSTFUH SN12C Investigative [1]
Breast adenocarcinoma DC7LYF1 MDA-MB-468 Investigative [33]
Colon carcinoma DCD65N0 KM12 Investigative [33]
Adenocarcinoma DC8JQT4 HCT116 Investigative [34]
High grade ovarian serous adenocarcinoma DC4R8AJ OVCAR-4 Investigative [34]
Lung adenocarcinoma DCRFQ2P EKVX Investigative [34]
Malignant melanoma DCHZ699 UACC62 Investigative [34]
Non-small cell lung carcinoma DC4N13L HOP-92 Investigative [34]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 DrugCom(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Thioguanine FDA Label
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6845).
5 Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 2015 Mar;115:9-16.
6 Pomalidomide FDA Label
7 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7348).
8 Immune effector cells produce lethal DNA damage in cells treated with a thiopurine. Cancer Res. 2009 Mar 15;69(6):2393-9.
9 ABC transporters and their role in nucleoside and nucleotide drug resistance. Biochem Pharmacol. 2012 Apr 15;83(8):1073-83.
10 Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57.
11 Involvement of the concentrative nucleoside transporter 3 and equilibrative nucleoside transporter 2 in the resistance of T-lymphoblastic cell lines to thiopurines. Biochem Biophys Res Commun. 2006 Apr 28;343(1):208-15.
12 Usefulness of thiopurine methyltransferase and thiopurine metabolite analysis in clinical practice in patients with inflammatory bowel diseases. Acta Gastroenterol Belg. 2010 Jul-Sep;73(3):331-5.
13 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.
14 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
15 CRISPR/Cas9-mediated gene knockout screens and target identification via whole-genome sequencing uncover host genes required for picornavirus infection. J Biol Chem. 2017 Jun 23;292(25):10664-10671. doi: 10.1074/jbc.M117.782425. Epub 2017 Apr 26.
16 Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. 2011 Mar;89(3):387-91. doi: 10.1038/clpt.2010.320. Epub 2011 Jan 26.
17 Petit E, Langouet S, Akhdar H, Nicolas-Nicolaz C, Guillouzo A, Morel F. Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes. Toxicol In Vitro. 2008;22(3):632-642. [PMID: 18222062]
18 Important role of caspase-8 for chemosensitivity of ALL cells. Clin Cancer Res. 2011 Dec 15;17(24):7605-13. doi: 10.1158/1078-0432.CCR-11-0513. Epub 2011 Oct 18.
19 The effect of 6-thioguanine on alternative splicing and antisense-mediated exon skipping treatment for duchenne muscular dystrophy. PLoS Curr. 2012 Dec 12;4:ecurrents.md.597d700f92eaa70de261ea0d91821377. doi: 10.1371/currents.md.597d700f92eaa70de261ea0d91821377.
20 The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clin Pharmacol Ther. 2006 Oct;80(4):375-83. doi: 10.1016/j.clpt.2006.07.002.
21 The effect of Msh2 knockdown on methylating agent induced toxicity in DNA glycosylase deficient cells. Toxicology. 2010 Jan 31;268(1-2):111-7. doi: 10.1016/j.tox.2009.12.008. Epub 2009 Dec 16.
22 The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites. Mol Cancer Ther. 2005 May;4(5):855-63.
23 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
24 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
25 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
26 Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78.
27 Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
28 Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide. Chem Res Toxicol. 2014 Jan 21;27(1):147-56. doi: 10.1021/tx4004215. Epub 2013 Dec 24.
29 Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
30 Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity. Chem Res Toxicol. 2019 Apr 15;32(4):589-602. doi: 10.1021/acs.chemrestox.8b00286. Epub 2019 Mar 15.
31 Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
32 A Dual Color Immunohistochemistry Assay for Measurement of Cereblon in Multiple Myeloma Patient Samples. Appl Immunohistochem Mol Morphol. 2016 Nov/Dec;24(10):695-702. doi: 10.1097/PAI.0000000000000246.
33 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
34 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.