General Information of Drug Combination (ID: DCOI9KK)

Drug Combination Name
Anastrozole Plicamycin
Indication
Disease Entry Status REF
Mixed endometrioid and clear cell 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: IGROV1
Zero Interaction Potency (ZIP) Score: 2.07
Bliss Independence Score: 2.88
Loewe Additivity Score: 3.35
LHighest Single Agent (HSA) Score: 3.32

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 [1]
Adenocarcinoma DCYXCKT A549 Investigative [1]
Adenocarcinoma DCIYDZ7 HT29 Investigative [1]
Adenocarcinoma DCUXZEP HCC-2998 Investigative [1]
Adenocarcinoma DC90XQF SW-620 Investigative [1]
Adult acute myeloid leukemia DCYY65A HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DCZ5850 MOLT-4 Investigative [1]
Amelanotic melanoma DCGG84H M14 Investigative [1]
Childhood T acute lymphoblastic leukemia DCUUUNL CCRF-CEM Investigative [1]
Chronic myelogenous leukemia DCQSU79 K-562 Investigative [1]
Clear cell renal cell carcinoma DCH73NY A498 Investigative [1]
Clear cell renal cell carcinoma DCROOSX 786-0 Investigative [1]
Cutaneous melanoma DCX2QXA SK-MEL-28 Investigative [1]
Glioblastoma DC85V8S SNB-75 Investigative [1]
High grade ovarian serous adenocarcinoma DCF7GQ8 OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DCVNK5E OVCAR-5 Investigative [1]
Large cell lung carcinoma DCNNX8T NCI-H460 Investigative [1]
Lung adenocarcinoma DCLLGQC HOP-62 Investigative [1]
Lung adenocarcinoma DC3PUDI MDA-MB-231 Investigative [1]
Lung adenocarcinoma DCKOAP8 NCI-H522 Investigative [1]
Malignant melanoma DCGXC2H LOX IMVI Investigative [1]
Melanoma DCD8ZMI MALME-3M Investigative [1]
Melanoma DCD1H8M SK-MEL-2 Investigative [1]
Melanoma DCM3WX3 UACC-257 Investigative [1]
Ovarian serous cystadenocarcinoma DC0S7IC SK-OV-3 Investigative [1]
Plasma cell myeloma DC3UO3N RPMI-8226 Investigative [1]
Prostate carcinoma DCJNKPH PC-3 Investigative [1]
Renal cell carcinoma DC0Q76N UO-31 Investigative [1]
Breast adenocarcinoma DC0L9MR MDA-MB-468 Investigative [28]
Carcinoma DC2PVBM RXF 393 Investigative [28]
Carcinoma DC6HWDC MCF7 Investigative [28]
Colon adenocarcinoma DC2OUMY COLO 205 Investigative [28]
Invasive ductal carcinoma DCKXCM0 HS 578T Investigative [28]
Invasive ductal carcinoma DCK29HU BT-549 Investigative [28]
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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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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.
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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.
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