General Information of Drug Combination (ID: DC1XZ4Z)

Drug Combination Name
Emetine Iloprost
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Emetine   DMCT2YF Iloprost   DMVPZBE
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 7.14
Bliss Independence Score: 7.14
Loewe Additivity Score: 8.58
LHighest Single Agent (HSA) Score: 8.62

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Emetine
Disease Entry ICD 11 Status REF
Hepatitis virus infection 1E50-1E51 Approved [2]
Emetine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
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Emetine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [7]
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Emetine Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) OT9QIHEQ RECK_HUMAN Decreases Expression [8]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [9]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Increases Degradation [10]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [8]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Decreases Expression [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [5]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Decreases Expression [5]
Microtubule-associated protein tau (MAPT) OTMTP2Z7 TAU_HUMAN Decreases Expression [12]
C-C motif chemokine 4 (CCL4) OT6B8P25 CCL4_HUMAN Decreases Expression [5]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Decreases Expression [5]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Expression [5]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
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⏷ Show the Full List of 15 DOT(s)
Indication(s) of Iloprost
Disease Entry ICD 11 Status REF
Pulmonary arterial hypertension BB01.0 Approved [3]
Pulmonary hypertension BB01 Approved [4]
Systemic sclerosis 4A42 Approved [4]
Iloprost Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Prostaglandin E2 receptor EP2 (PTGER2) TT1ZAVI PE2R2_HUMAN Agonist [13]
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Iloprost Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporting polypeptide 2A1 (SLCO2A1) DT021JD SO2A1_HUMAN Substrate [14]
Organic anion transporting polypeptide 3A1 (SLCO3A1) DTVNRXW SO3A1_HUMAN Substrate [15]
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Iloprost Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Angiopoietin-2 (ANGPT2) OTEQK65P ANGP2_HUMAN Increases Expression [16]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [17]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [17]
Fibroblast growth factor 2 (FGF2) OT7YUJ9F FGF2_HUMAN Increases Expression [16]
L-selectin (SELL) OT6RAJZR LYAM1_HUMAN Decreases Expression [17]
DNA-binding protein inhibitor ID-1 (ID1) OTKGNZN5 ID1_HUMAN Increases Expression [18]
Prostacyclin receptor (PTGIR) OTWTABYM PI2R_HUMAN Affects Binding [19]
Angiopoietin-1 (ANGPT1) OTVZ1NG3 ANGP1_HUMAN Increases Expression [16]
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⏷ Show the Full List of 8 DOT(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 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: 1966).
4 Iloprost FDA Label
5 Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
6 Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia. 2005 Feb;46(2):224-35.
7 Metabolism of ipecac alkaloids cephaeline and emetine by human hepatic microsomal cytochrome P450s, and their inhibitory effects on P450 enzyme activities. Biol Pharm Bull. 2001 Jun;24(6):678-82.
8 Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways. Chem Biol Interact. 2015 Dec 5;242:25-33. doi: 10.1016/j.cbi.2015.08.014. Epub 2015 Aug 30.
9 Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
10 IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression. Mol Cancer. 2023 May 29;22(1):88. doi: 10.1186/s12943-023-01792-0.
11 Apoptosis induces Bcl-XS and cleaved Bcl-XL in chronic lymphocytic leukaemia. Biochem Biophys Res Commun. 2011 Feb 18;405(3):480-5. doi: 10.1016/j.bbrc.2011.01.057. Epub 2011 Jan 20.
12 Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener. 2006 Jul 26;1:6. doi: 10.1186/1750-1326-1-6.
13 Exploration of prostanoid receptor subtype regulating estradiol and prostaglandin E2 induction of spinophilin in developing preoptic area neurons. Neuroscience. 2007 May 25;146(3):1117-27.
14 Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9.
15 Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97.
16 Prostacyclin receptor up-regulates the expression of angiogenic genes in human endometrium via cross talk with epidermal growth factor Receptor and the extracellular signaling receptor kinase 1/2 pathway. Endocrinology. 2006 Apr;147(4):1697-705. doi: 10.1210/en.2005-1073. Epub 2005 Dec 22.
17 The response of skin perfusion and of rheological and immunological variables to intravenous prostanoid administration in Raynaud's phenomenon secondary to collagenosis. Vasa. 2005 Nov;34(4):243-9. doi: 10.1024/0301-1526.34.4.243.
18 Smad-dependent and smad-independent induction of id1 by prostacyclin analogues inhibits proliferation of pulmonary artery smooth muscle cells in vitro and in vivo. Circ Res. 2010 Jul 23;107(2):252-62. doi: 10.1161/CIRCRESAHA.109.209940. Epub 2010 Jun 3.
19 Investigation of a functional requirement for isoprenylation by the human prostacyclin receptor. Eur J Biochem. 2002 Mar;269(6):1714-25. doi: 10.1046/j.1432-1327.2002.02817.x.