General Information of Drug Combination (ID: DCCUG75)

Drug Combination Name
Arfolitixorin Plicamycin
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Arfolitixorin   DMIXMYK 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: A549
Zero Interaction Potency (ZIP) Score: 2.38
Bliss Independence Score: 0.53
Loewe Additivity Score: 0.45
LHighest Single Agent (HSA) Score: 0.46

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Arfolitixorin
Disease Entry ICD 11 Status REF
Colorectal cancer 2B91.Z Phase 3 [2]
Indication(s) of Plicamycin
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [3]
Testicular cancer 2C80 Approved [3]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [4]
Lung cancer 2C25.0 Investigative [5]
Ovarian cancer 2C73 Investigative [5]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [7]
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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 [8]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [9]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [9]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [9]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [10]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [11]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [6]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [12]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [13]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [14]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [6]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [15]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [12]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [16]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [17]
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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 DCNUH3W HL-60(TB) Investigative [18]
Adult T acute lymphoblastic leukemia DCHQNJA MOLT-4 Investigative [18]
Astrocytoma DCAX9WE U251 Investigative [18]
Chronic myelogenous leukemia DCJIOHM K-562 Investigative [18]
Clear cell renal cell carcinoma DCXGX2G A498 Investigative [18]
Clear cell renal cell carcinoma DCE48U2 CAKI-1 Investigative [18]
Glioblastoma DCU3RMA SNB-75 Investigative [18]
Glioma DC0BYLO SF-268 Investigative [18]
Glioma DCBTP00 SF-539 Investigative [18]
Plasma cell myeloma DCPNN7J RPMI-8226 Investigative [18]
Breast adenocarcinoma DCLVOLC MDA-MB-468 Investigative [19]
Carcinoma DCLR5YE RXF 393 Investigative [19]
Colon carcinoma DC114D2 KM12 Investigative [19]
Invasive ductal carcinoma DC9HH1T BT-549 Investigative [19]
Invasive ductal carcinoma DCQ0CNF HS 578T Investigative [19]
Adenocarcinoma DC9CFYG OVCAR3 Investigative [1]
Adenocarcinoma DCGN1ZC HCT116 Investigative [1]
Adenocarcinoma DCPVDE6 HCC-2998 Investigative [1]
Adenocarcinoma DCW0WOI HT29 Investigative [1]
Amelanotic melanoma DCVIR4L MDA-MB-435 Investigative [1]
Cutaneous melanoma DCD67ZE SK-MEL-28 Investigative [1]
Cutaneous melanoma DC2CMWL SK-MEL-5 Investigative [1]
High grade ovarian serous adenocarcinoma DCXY2YC OVCAR-4 Investigative [1]
High grade ovarian serous adenocarcinoma DCVHNT7 OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DCKVOC5 OVCAR-5 Investigative [1]
Large cell lung carcinoma DCO9KER NCI-H460 Investigative [1]
Lung adenocarcinoma DCZ136F HOP-62 Investigative [1]
Lung adenocarcinoma DCJOF1H EKVX Investigative [1]
Lung adenocarcinoma DCOMOI5 MDA-MB-231 Investigative [1]
Lung adenocarcinoma DC5FKCX NCI-H522 Investigative [1]
Malignant melanoma DC1WPAR LOX IMVI Investigative [1]
Malignant melanoma DC9EYB0 UACC62 Investigative [1]
Melanoma DCSEYSD MALME-3M Investigative [1]
Melanoma DC8GC5Q UACC-257 Investigative [1]
Melanoma DC893YD SK-MEL-2 Investigative [1]
Minimally invasive lung adenocarcinoma DCC5SVQ NCI-H322M Investigative [1]
Mixed endometrioid and clear cell carcinoma DCJ5WHD IGROV1 Investigative [1]
Ovarian serous cystadenocarcinoma DCN8VSD SK-OV-3 Investigative [1]
Prostate carcinoma DCUAZVC PC-3 Investigative [1]
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⏷ Show the Full List of 39 DrugCom(s)

References

1 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.
2 ClinicalTrials.gov (NCT03750786) A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer (AGENT). U.S. National Institutes of Health.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 8394).
5 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
6 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.
7 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
8 SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
9 Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression. Toxicol Appl Pharmacol. 2014 Oct 1;280(1):138-48.
10 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.
11 Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter. Gene. 2014 Feb 15;536(1):135-44. doi: 10.1016/j.gene.2013.11.053. Epub 2013 Dec 4.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.
19 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.