General Information of Drug Combination (ID: DC2PVBM)

Drug Combination Name
Anastrozole Plicamycin
Indication
Disease Entry Status REF
Carcinoma Investigative [1]
Component Drugs Anastrozole   DMNP60F 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: RXF 393
Zero Interaction Potency (ZIP) Score: 2.08
Bliss Independence Score: 5.43
Loewe Additivity Score: 6.2
LHighest Single Agent (HSA) Score: 5.93

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Anastrozole
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Estrogen-receptor positive breast cancer N.A. Approved [3]
Obesity 5B81 Approved [3]
Anastrozole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [7]
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Anastrozole Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Putative sodium-coupled neutral amino acid transporter 7 (SLC38A7) DT2EGUN S38A7_HUMAN Substrate [8]
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Anastrozole Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [9]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [9]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [9]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [9]
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⏷ Show the Full List of 6 DME(s)
Anastrozole Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [10]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Decreases Expression [11]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [12]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Decreases Activity [13]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Decreases Expression [14]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [15]
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⏷ Show the Full List of 6 DOT(s)
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 [5]
Lung cancer 2C25.0 Investigative [6]
Ovarian cancer 2C73 Investigative [6]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [17]
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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 [18]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [19]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [19]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [19]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [20]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [20]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [21]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [16]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [22]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [23]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [24]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [16]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [25]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [22]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [26]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [27]
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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
Adenocarcinoma DCYE4A6 DU-145 Investigative [28]
Adenocarcinoma DCYXCKT A549 Investigative [28]
Adenocarcinoma DCIYDZ7 HT29 Investigative [28]
Adenocarcinoma DCUXZEP HCC-2998 Investigative [28]
Adenocarcinoma DC90XQF SW-620 Investigative [28]
Adult acute myeloid leukemia DCYY65A HL-60(TB) Investigative [28]
Adult T acute lymphoblastic leukemia DCZ5850 MOLT-4 Investigative [28]
Amelanotic melanoma DCGG84H M14 Investigative [28]
Childhood T acute lymphoblastic leukemia DCUUUNL CCRF-CEM Investigative [28]
Chronic myelogenous leukemia DCQSU79 K-562 Investigative [28]
Clear cell renal cell carcinoma DCH73NY A498 Investigative [28]
Clear cell renal cell carcinoma DCROOSX 786-0 Investigative [28]
Cutaneous melanoma DCX2QXA SK-MEL-28 Investigative [28]
Glioblastoma DC85V8S SNB-75 Investigative [28]
High grade ovarian serous adenocarcinoma DCF7GQ8 OVCAR-8 Investigative [28]
High grade ovarian serous adenocarcinoma DCVNK5E OVCAR-5 Investigative [28]
Large cell lung carcinoma DCNNX8T NCI-H460 Investigative [28]
Lung adenocarcinoma DCLLGQC HOP-62 Investigative [28]
Lung adenocarcinoma DC3PUDI MDA-MB-231 Investigative [28]
Lung adenocarcinoma DCKOAP8 NCI-H522 Investigative [28]
Malignant melanoma DCGXC2H LOX IMVI Investigative [28]
Melanoma DCD8ZMI MALME-3M Investigative [28]
Melanoma DCD1H8M SK-MEL-2 Investigative [28]
Melanoma DCM3WX3 UACC-257 Investigative [28]
Mixed endometrioid and clear cell carcinoma DCOI9KK IGROV1 Investigative [28]
Ovarian serous cystadenocarcinoma DC0S7IC SK-OV-3 Investigative [28]
Plasma cell myeloma DC3UO3N RPMI-8226 Investigative [28]
Prostate carcinoma DCJNKPH PC-3 Investigative [28]
Renal cell carcinoma DC0Q76N UO-31 Investigative [28]
Breast adenocarcinoma DC0L9MR MDA-MB-468 Investigative [1]
Carcinoma DC6HWDC MCF7 Investigative [1]
Colon adenocarcinoma DC2OUMY COLO 205 Investigative [1]
Invasive ductal carcinoma DCKXCM0 HS 578T Investigative [1]
Invasive ductal carcinoma DCK29HU BT-549 Investigative [1]
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⏷ Show the Full List of 34 DrugCom(s)

References

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2 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: 5137).
3 Anastrozole FDA Label
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 8394).
6 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
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8 Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2. Clin Pharmacol Ther. 2019 Jan 16.
9 In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69.
10 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.
11 Aromatase inhibitors: cellular and molecular effects. J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9. doi: 10.1016/j.jsbmb.2005.04.010.
12 Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res. 2005 Apr 15;11(8):2809-21. doi: 10.1158/1078-0432.CCR-04-2187.
13 Assessment of Five Pesticides as Endocrine-Disrupting Chemicals: Effects on Estrogen Receptors and Aromatase. Int J Environ Res Public Health. 2022 Feb 10;19(4):1959. doi: 10.3390/ijerph19041959.
14 Inhibition of estrogen receptor reduces connexin 43 expression in breast cancers. Toxicol Appl Pharmacol. 2018 Jan 1;338:182-190. doi: 10.1016/j.taap.2017.11.020. Epub 2017 Nov 24.
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16 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.
17 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
18 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.
19 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.
20 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.
21 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.
22 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.
23 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.
24 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.
25 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.
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27 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.
28 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.