General Information of Drug Combination (ID: DCQN1R8)

Drug Combination Name
Dacarbazine Pomalidomide
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Dacarbazine   DMNPZL4 Pomalidomide   DMTGBAX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HCC-2998
Zero Interaction Potency (ZIP) Score: 0.82
Bliss Independence Score: 8.69
Loewe Additivity Score: 5.32
LHighest Single Agent (HSA) Score: 6.32

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Dacarbazine
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [2]
Astrocytoma 2A00.0Y Approved [2]
Brain disease 8C70-8E61 Approved [2]
Central nervous system disease 8A04-8D87 Approved [2]
Glioblastoma 2A00 Approved [2]
Gliosarcoma N.A. Approved [2]
Melanoma 2C30 Approved [3]
Classic Hodgkin lymphoma N.A. Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
Dacarbazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Breaker [7]
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Dacarbazine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [9]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [10]
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Dacarbazine Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Increases Expression [11]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [6]
Interferon regulatory factor 1 (IRF1) OT43DI6J IRF1_HUMAN Increases Expression [12]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Decreases Activity [13]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Response To Substance [14]
DNA repair nuclease/redox regulator APEX1 (APEX1) OT53OI14 APEX1_HUMAN Increases Response To Substance [15]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Decreases Response To Substance [16]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Response To Substance [17]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Response To Substance [17]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Affects Response To Substance [18]
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) OTS3FVTY M3K1_HUMAN Decreases Response To Substance [17]
Erythropoietin (EPO) OTZ90CN4 EPO_HUMAN Decreases Response To Substance [19]
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⏷ Show the Full List of 12 DOT(s)
Indication(s) of Pomalidomide
Disease Entry ICD 11 Status REF
Plasma cell myeloma 2A83.1 Approved [4]
Systemic sclerosis 4A42 Approved [5]
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 [20]
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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 [21]
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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 [22]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [23]
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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 [24]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Secretion [25]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Secretion [25]
Granulocyte colony-stimulating factor (CSF3) OT9GC6TP CSF3_HUMAN Increases Secretion [25]
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Decreases Expression [26]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [25]
Erythroid transcription factor (GATA1) OTX1R7O1 GATA1_HUMAN Decreases Expression [25]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Decreases Expression [25]
Transcription factor PU.1 (SPI1) OTVCA1D0 SPI1_HUMAN Increases Expression [25]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [25]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Affects Expression [26]
Endothelial transcription factor GATA-2 (GATA2) OTBP2QQ2 GATA2_HUMAN Decreases Expression [25]
Rhombotin-2 (LMO2) OTCC370G RBTN2_HUMAN Decreases Expression [25]
Interleukin-13 (IL13) OTI4YS3Y IL13_HUMAN Decreases Secretion [25]
DNA-binding protein inhibitor ID-1 (ID1) OTKGNZN5 ID1_HUMAN Increases Expression [25]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Increases Expression [25]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [25]
DNA-binding protein inhibitor ID-2 (ID2) OT0U1D53 ID2_HUMAN Increases Expression [25]
Krueppel-like factor 1 (KLF1) OT1FK08U KLF1_HUMAN Decreases Expression [25]
CCAAT/enhancer-binding protein epsilon (CEBPE) OTKZA25M CEBPE_HUMAN Increases Expression [25]
Transcription factor NF-E2 45 kDa subunit (NFE2) OTLM94BI NFE2_HUMAN Decreases Expression [25]
Zinc finger protein Gfi-1b (GFI1B) OTRDW8YO GFI1B_HUMAN Decreases Expression [25]
Zinc finger protein Gfi-1 (GFI1) OT9HB9H8 GFI1_HUMAN Increases Expression [25]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [27]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Oxidation [24]
Cytochrome P450 2J2 (CYP2J2) OTJBTEH8 CP2J2_HUMAN Increases Oxidation [24]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [28]
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⏷ 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
Adenocarcinoma DCVFAEC OVCAR3 Investigative [1]
Adenocarcinoma DCV3DR9 HCT116 Investigative [1]
Amelanotic melanoma DCYOO9G M14 Investigative [1]
Amelanotic melanoma DC82U5Z MDA-MB-435 Investigative [1]
Childhood T acute lymphoblastic leukemia DCZIREI CCRF-CEM Investigative [1]
Clear cell renal cell carcinoma DCVGH9I 786-0 Investigative [1]
Clear cell renal cell carcinoma DC2JPD6 CAKI-1 Investigative [1]
Glioblastoma DCOLXFO SNB-75 Investigative [1]
Glioma DCJEP9E SF-295 Investigative [1]
High grade ovarian serous adenocarcinoma DC6O317 NCI\\/ADR-RES Investigative [1]
Lung adenocarcinoma DCL9STY EKVX Investigative [1]
Malignant melanoma DCLK467 UACC62 Investigative [1]
Pleural epithelioid mesothelioma DCLUQEH NCI-H226 Investigative [1]
Renal cell carcinoma DC4DQYS SN12C Investigative [1]
Colon carcinoma DCC250F KM12 Investigative [29]
Invasive ductal carcinoma DCY3692 HS 578T Investigative [29]
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⏷ Show the Full List of 16 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 Dacarbazine FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075259.
4 Pomalidomide FDA Label
5 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).
6 Dacarbazine causes transcriptional up-regulation of interleukin 8 and vascular endothelial growth factor in melanoma cells: a possible escape mechanism from chemotherapy. Mol Cancer Ther. 2003 Aug;2(8):753-63.
7 Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mono... Melanoma Res. 2011 Dec;21(6):502-8.
8 Study on mesenchymal stem cells mediated enzyme-prodrug gene CYP1A2 targeting anti-tumor effect. Zhonghua Xue Ye Xue Za Zhi. 2009 Oct;30(10):667-71.
9 Metabolic activation of dacarbazine by human cytochromes P450: the role of CYP1A1, CYP1A2, and CYP2E1. Clin Cancer Res. 1999 Aug;5(8):2192-7.
10 Role of cytochrome P450 isoenzymes in metabolism of O(6)-benzylguanine: implications for dacarbazine activation. Clin Cancer Res. 2001 Dec;7(12):4239-44.
11 Serum bcl-2 and survivin levels in melanoma. Melanoma Res. 2004 Dec;14(6):543-6. doi: 10.1097/00008390-200412000-00017.
12 CD69 on CD56+ NK cells and response to chemoimmunotherapy in metastatic melanoma. Eur J Clin Invest. 2007 Nov;37(11):887-96. doi: 10.1111/j.1365-2362.2007.01873.x.
13 Pharmacokinetic, biochemical and clinical effects of dimethyltriazenoimidazole-4-carboxamide-bischloroethylnitrosourea combination therapy in patients with advanced breast cancer. Int J Cancer. 2003 Feb 20;103(5):686-92. doi: 10.1002/ijc.10849.
14 Mcl-1 antisense therapy chemosensitizes human melanoma in a SCID mouse xenotransplantation model. J Invest Dermatol. 2003 Jun;120(6):1081-6. doi: 10.1046/j.1523-1747.2003.12252.x.
15 Impairment of APE1 function enhances cellular sensitivity to clinically relevant alkylators and antimetabolites. Mol Cancer Res. 2009 Jun;7(6):897-906. doi: 10.1158/1541-7786.MCR-08-0519. Epub 2009 May 26.
16 Glut-1 as a therapeutic target: increased chemoresistance and HIF-1-independent link with cell turnover is revealed through COMPARE analysis and metabolomic studies. Cancer Chemother Pharmacol. 2008 Mar;61(3):377-93. doi: 10.1007/s00280-007-0480-1. Epub 2007 May 23.
17 Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo. J Clin Oncol. 2004 Jun 1;22(11):2092-100. doi: 10.1200/JCO.2004.11.070. Epub 2004 May 3.
18 Clusterin regulates drug-resistance in melanoma cells. J Invest Dermatol. 2005 Jun;124(6):1300-7. doi: 10.1111/j.0022-202X.2005.23720.x.
19 Functional erythropoietin autocrine loop in melanoma. Am J Pathol. 2005 Mar;166(3):823-30. doi: 10.1016/S0002-9440(10)62303-6.
20 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
21 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
22 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.
23 Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
24 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.
25 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.
26 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.
27 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.
28 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.
29 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.