General Information of Drug Combination (ID: DCACRO0)

Drug Combination Name
Anastrozole Bleomycin
Indication
Disease Entry Status REF
Lung adenocarcinoma Investigative [1]
Component Drugs Anastrozole   DMNP60F Bleomycin   DMNER5S
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: EKVX
Zero Interaction Potency (ZIP) Score: 7.78
Bliss Independence Score: 8.62
Loewe Additivity Score: 7.57
LHighest Single Agent (HSA) Score: 11.16

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 [6]
------------------------------------------------------------------------------------
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 [7]
------------------------------------------------------------------------------------
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 [8]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [8]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [8]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [8]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [8]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [8]
------------------------------------------------------------------------------------
⏷ 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 [9]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Decreases Expression [10]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [11]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Decreases Activity [12]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Decreases Expression [13]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [14]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DOT(s)
Indication(s) of Bleomycin
Disease Entry ICD 11 Status REF
Cervical cancer 2C77.0 Approved [4]
Head and neck cancer 2D42 Approved [4]
Hodgkin lymphoma 2B30 Approved [5]
Penile cancer N.A. Approved [4]
Testicular germ cell tumor N.A. Approved [4]
Classic Hodgkin lymphoma N.A. Investigative [4]
Follicular lymphoma 2A80 Investigative [4]
Bleomycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Breaker [19]
------------------------------------------------------------------------------------
Bleomycin Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Bleomycin hydrolase (BLMH) DECH1VP BLMH_HUMAN Metabolism [20]
------------------------------------------------------------------------------------
Bleomycin Interacts with 41 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bleomycin hydrolase (BLMH) OT2QPWQJ BLMH_HUMAN Affects Response To Substance [21]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Increases Expression [22]
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Expression [22]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [22]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Increases Expression [23]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases Expression [23]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [23]
C-X-C motif chemokine 2 (CXCL2) OTEJCYMY CXCL2_HUMAN Increases Expression [23]
Mucin-5AC (MUC5AC) OTJV8O04 MUC5A_HUMAN Increases Expression [23]
Proheparin-binding EGF-like growth factor (HBEGF) OTLU00JS HBEGF_HUMAN Increases Expression [23]
Transmembrane protein 250 (TMEM250) OTLJ4G5G TM250_HUMAN Increases Expression [15]
Suppressor of cytokine signaling 1 (SOCS1) OTWA9KFU SOCS1_HUMAN Decreases Expression [24]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [25]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [16]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [26]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [16]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [16]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [27]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [16]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [28]
Cathepsin S (CTSS) OT3PXIPM CATS_HUMAN Increases Expression [29]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [30]
Max-interacting protein 1 (MXI1) OTUQ9E0D MXI1_HUMAN Decreases Expression [15]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Increases Expression [16]
Unconventional myosin-Ie (MYO1E) OTM9YSIZ MYO1E_HUMAN Decreases Expression [15]
Transcription intermediary factor 1-beta (TRIM28) OTE38OBF TIF1B_HUMAN Increases Phosphorylation [25]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [25]
Structural maintenance of chromosomes protein 1A (SMC1A) OT9ZMRK9 SMC1A_HUMAN Increases Phosphorylation [25]
7SK snRNA methylphosphate capping enzyme (MEPCE) OTRBQEYP MEPCE_HUMAN Increases Expression [15]
Transmembrane protein 87A (TMEM87A) OT8ATDVX TM87A_HUMAN Increases Expression [15]
Terminal nucleotidyltransferase 4B (TENT4B) OTUF6FWW PAPD5_HUMAN Decreases Expression [15]
Lipase member H (LIPH) OTRGYLKL LIPH_HUMAN Decreases Expression [15]
Abasic site processing protein HMCES (HMCES) OTVRDL6U HMCES_HUMAN Decreases Expression [15]
Small integral membrane protein 14 (SMIM14) OT47IF19 SIM14_HUMAN Decreases Expression [15]
Kelch-like protein 42 (KLHL42) OTK6WARI KLH42_HUMAN Increases Expression [15]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2) OT9I1XUO CEIP2_HUMAN Decreases Expression [15]
ERBB receptor feedback inhibitor 1 (ERRFI1) OT7VZ2IZ ERRFI_HUMAN Decreases Expression [15]
Transmembrane and coiled-coil domain protein 3 (TMCC3) OTAIQ6V6 TMCC3_HUMAN Decreases Expression [15]
Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5) OT27CCUF SIAT9_HUMAN Decreases Expression [15]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [31]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Affects Response To Substance [32]
------------------------------------------------------------------------------------
⏷ Show the Full List of 41 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCL07Y4 DU-145 Investigative [1]
Adenocarcinoma DCJPK9M OVCAR3 Investigative [1]
Adenocarcinoma DCBMWFH A549 Investigative [1]
Adenocarcinoma DCP3S2A HCC-2998 Investigative [1]
Adenocarcinoma DC8Y7M4 SW-620 Investigative [1]
Adenocarcinoma DCA229E HCT116 Investigative [1]
Adult acute myeloid leukemia DCBKWEC HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DC0E2Y1 MOLT-4 Investigative [1]
Amelanotic melanoma DCLKWT5 MDA-MB-435 Investigative [1]
Anaplastic large cell lymphoma DCGDFI6 SR Investigative [1]
Astrocytoma DCGH2PU SNB-19 Investigative [1]
Childhood T acute lymphoblastic leukemia DC36ZL2 CCRF-CEM Investigative [1]
Chronic myelogenous leukemia DC9KFJA K-562 Investigative [1]
Clear cell renal cell carcinoma DCDYXVD TK-10 Investigative [1]
Cutaneous melanoma DCLI8G8 SK-MEL-28 Investigative [1]
Cutaneous melanoma DCMR319 SK-MEL-5 Investigative [1]
Glioblastoma DCX0LVX SNB-75 Investigative [1]
Glioma DCJBTUD SF-268 Investigative [1]
Glioma DC47PXH SF-539 Investigative [1]
Glioma DCZ98V0 SF-295 Investigative [1]
High grade ovarian serous adenocarcinoma DCYZ7UV OVCAR-5 Investigative [1]
High grade ovarian serous adenocarcinoma DC98VLY OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DC6N2AK OVCAR-4 Investigative [1]
Large cell lung carcinoma DC1DN9R NCI-H460 Investigative [1]
Lung adenocarcinoma DC68RV7 MDA-MB-231 Investigative [1]
Lung adenocarcinoma DCNP4GV HOP-62 Investigative [1]
Lung adenocarcinoma DCKN7LD NCI-H522 Investigative [1]
Malignant melanoma DCLRV8D UACC62 Investigative [1]
Malignant melanoma DCIB7EA LOX IMVI Investigative [1]
Melanoma DCENW07 UACC-257 Investigative [1]
Melanoma DCQYOCE SK-MEL-2 Investigative [1]
Melanoma DC2M1CK MALME-3M Investigative [1]
Mixed endometrioid and clear cell carcinoma DC4ZJ08 IGROV1 Investigative [1]
Non-small cell lung carcinoma DCWQ6AD HOP-92 Investigative [1]
Ovarian serous cystadenocarcinoma DC1WGMM SK-OV-3 Investigative [1]
Papillary renal cell carcinoma DCY21HT ACHN Investigative [1]
Plasma cell myeloma DCUPAPJ RPMI-8226 Investigative [1]
Prostate carcinoma DCTJ00V PC-3 Investigative [1]
Renal cell carcinoma DCULZVW SN12C Investigative [1]
Breast adenocarcinoma DCKWBA8 MDA-MB-468 Investigative [33]
Carcinoma DC63HP7 RXF 393 Investigative [33]
Colon adenocarcinoma DCGVFDE COLO 205 Investigative [33]
Colon carcinoma DC8RNNV KM12 Investigative [33]
Invasive ductal carcinoma DCVRVC5 HS 578T Investigative [33]
------------------------------------------------------------------------------------
⏷ Show the Full List of 44 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 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 Bleomycin FDA Label
5 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
6 Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:945-8.
7 Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2. Clin Pharmacol Ther. 2019 Jan 16.
8 In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69.
9 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.
10 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.
11 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.
12 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.
13 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.
14 Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists. J Clin Oncol. 2005 Apr 10;23(11):2477-92. doi: 10.1200/JCO.2005.07.559. Epub 2005 Mar 14.
15 Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
16 Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cells. Cell Biol Toxicol. 2022 Aug;38(4):557-575. doi: 10.1007/s10565-022-09698-1. Epub 2022 Mar 10.
17 An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents. Cancer Res. 2002 Oct 15;62(20):5888-96.
18 XRCC1 deficiency sensitizes human lung epithelial cells to genotoxicity by crocidolite asbestos and Libby amphibole. Environ Health Perspect. 2010 Dec;118(12):1707-13. doi: 10.1289/ehp.1002312. Epub 2010 Aug 11.
19 Bleomycin and talisomycin sequence-specific strand scission of DNA: a mechanism of double-strand cleavage. Cancer Res. 1982 Jul;42(7):2779-85.
20 The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage. Mutat Res. 1998 Oct 12;421(1):1-7.
21 Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity. Carcinogenesis. 2002 Jun;23(6):1003-8. doi: 10.1093/carcin/23.6.1003.
22 Age-dependent basal level and induction capacity of copper-zinc and manganese superoxide dismutase and other scavenging enzyme activities in leukocytes from young and elderly adults. Am J Pathol. 1993 Jul;143(1):312-20.
23 Agents associated with lung inflammation induce similar responses in NCI-H292 lung epithelial cells. Toxicol In Vitro. 2008 Oct;22(7):1782-8.
24 Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
25 Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One. 2014 Jun 16;9(6):e97969. doi: 10.1371/journal.pone.0097969. eCollection 2014.
26 Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure. J Immunol. 1993 May 1;150(9):4188-96.
27 Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: Caspase-dependent and independent apoptotic pathways. Chem Biol Interact. 2016 Mar 5;247:1-10. doi: 10.1016/j.cbi.2016.01.012. Epub 2016 Jan 29.
28 Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.
29 Radiation-induced cathepsin S is involved in radioresistance. Int J Cancer. 2009 Apr 15;124(8):1794-801. doi: 10.1002/ijc.24095.
30 Bleomycin-induced nuclear factor-kappaB activation in human bronchial epithelial cells involves the phosphorylation of glycogen synthase kinase 3beta. Toxicol Lett. 2009 Jun 22;187(3):194-200. doi: 10.1016/j.toxlet.2009.02.023. Epub 2009 Mar 13.
31 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
32 DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008 Jan;28(2):752-71. doi: 10.1128/MCB.01799-07. Epub 2007 Nov 8.
33 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.