General Information of Drug Combination (ID: DC46V0X)

Drug Combination Name
Ruxolitinib Plicamycin
Indication
Disease Entry Status REF
Plasma cell myeloma Investigative [1]
Component Drugs Ruxolitinib   DM7Q98D Plicamycin   DM7C8YV
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: RPMI-8226
Zero Interaction Potency (ZIP) Score: 33.72
Bliss Independence Score: 32.88
Loewe Additivity Score: 29.31
LHighest Single Agent (HSA) Score: 27.73

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ruxolitinib
Disease Entry ICD 11 Status REF
Essential thrombocythemia 3B63.1Z Approved [2]
High-risk myelofibrosis 2A20.2 Approved [3]
Myelofibrosis 2A22 Approved [4]
Myeloproliferative neoplasm 2A20 Approved [5]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [6]
Pancreatic cancer 2C10 Phase 3 [3]
Atopic dermatitis EA80 Phase 1/2 [7]
Vitiligo ED63.0 Phase 1/2 [7]
Ruxolitinib Interacts with 5 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Janus kinase 2 (JAK-2) TTRMX3V JAK2_HUMAN Modulator [10]
Janus kinase 1 (JAK-1) TT6DM01 JAK1_HUMAN Modulator [10]
Urokinase plasminogen activator surface receptor (PLAUR) TTPRL03 UPAR_HUMAN Inhibitor [11]
HUMAN janus kinase 1 (JAK-1) TTWKB01 JAK1_HUMAN Inhibitor [12]
HUMAN janus kinase 2 (JAK-2) TT0F5HE JAK2_HUMAN Inhibitor [12]
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Ruxolitinib Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Mitogen-activated protein kinase 14 (MAPK14) OT5TCO3O MK14_HUMAN Increases ADR [13]
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Indication(s) of Plicamycin
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [4]
Testicular cancer 2C80 Approved [4]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [8]
Lung cancer 2C25.0 Investigative [9]
Ovarian cancer 2C73 Investigative [9]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [15]
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Plicamycin Interacts with 16 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Decreases Expression [16]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [17]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [17]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [17]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [18]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [18]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [19]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [14]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [20]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [21]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [22]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [14]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [23]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [20]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [24]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [25]
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⏷ Show the Full List of 16 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCAK2AJ HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DCVQCXX MOLT-4 Investigative [1]
Anaplastic large cell lymphoma DC7I3LT SR Investigative [1]
Astrocytoma DCMRJUI U251 Investigative [1]
Astrocytoma DCP0UVE SNB-19 Investigative [1]
Childhood T acute lymphoblastic leukemia DCSZ29A CCRF-CEM Investigative [1]
Chronic myelogenous leukemia DCT8TVE K-562 Investigative [1]
Clear cell renal cell carcinoma DCMGNCV TK-10 Investigative [1]
Clear cell renal cell carcinoma DCYJKW4 A498 Investigative [1]
Clear cell renal cell carcinoma DC0MDOV 786-0 Investigative [1]
Clear cell renal cell carcinoma DCN1A5J CAKI-1 Investigative [1]
Glioma DCFUV3H SF-539 Investigative [1]
Glioma DCOXTVC SF-295 Investigative [1]
Papillary renal cell carcinoma DCFL78I ACHN Investigative [1]
Carcinoma DC6XBKU MCF7 Investigative [26]
Colon adenocarcinoma DC4G2QL COLO 205 Investigative [26]
Colon carcinoma DC5BO42 KM12 Investigative [26]
Invasive ductal carcinoma DC29QEU T-47D Investigative [26]
Invasive ductal carcinoma DCR4RZQ BT-549 Investigative [26]
Invasive ductal carcinoma DCDFJDH HS 578T Investigative [26]
Adenocarcinoma DCROKN8 OVCAR3 Investigative [27]
Adenocarcinoma DC47ZNK SW-620 Investigative [27]
Adenocarcinoma DCI2M9Q HCT-15 Investigative [27]
Adenocarcinoma DC0848B HCT116 Investigative [27]
Adenocarcinoma DCL0QDL HCC-2998 Investigative [27]
Amelanotic melanoma DCYYZBV MDA-MB-435 Investigative [27]
Cutaneous melanoma DCD1MDI SK-MEL-28 Investigative [27]
Cutaneous melanoma DC9YSLR SK-MEL-5 Investigative [27]
High grade ovarian serous adenocarcinoma DCULFUI OVCAR-5 Investigative [27]
High grade ovarian serous adenocarcinoma DC0QRAK OVCAR-8 Investigative [27]
High grade ovarian serous adenocarcinoma DCS3AML OVCAR-4 Investigative [27]
Large cell lung carcinoma DCFY4S1 NCI-H460 Investigative [27]
Melanoma DCK0CZ0 UACC-257 Investigative [27]
Melanoma DCB9JW5 SK-MEL-2 Investigative [27]
Melanoma DC2XXRV MALME-3M Investigative [27]
Minimally invasive lung adenocarcinoma DCZSVC1 NCI-H322M Investigative [27]
Non-small cell lung carcinoma DC700ZP HOP-92 Investigative [27]
Prostate carcinoma DCA079H PC-3 Investigative [27]
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⏷ Show the Full List of 38 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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 5688).
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 Ruxolitinib FDA Label
6 Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 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: 8394).
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14 The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
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18 Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem. 2007 Jan 26;282(4):2615-25. doi: 10.1074/jbc.M606203200. Epub 2006 Nov 22.
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20 Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression. Chem Biol Interact. 2010 Jan 5;183(1):181-6. doi: 10.1016/j.cbi.2009.09.018.
21 Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro. Lung. 2004;182(4):251-64. doi: 10.1007/s00408-004-2507-2.
22 The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
23 CREB/Sp1-mediated MCL1 expression and NFB-mediated ABCB1 expression modulate the cytotoxicity of daunorubicin in chronic myeloid leukemia cells. Toxicol Appl Pharmacol. 2022 Jan 15;435:115847. doi: 10.1016/j.taap.2021.115847. Epub 2021 Dec 25.
24 Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
25 Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
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