General Information of Drug Combination (ID: DC4G9YW)

Drug Combination Name
Nilutamide Flutamide
Indication
Disease Entry Status REF
Prostate Cancer Phase 3 [1]
Component Drugs Nilutamide   DMFN07X Flutamide   DMK0O7U
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Nilutamide
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Approved [2]
Nilutamide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Androgen receptor (AR) TTS64P2 ANDR_HUMAN Antagonist [4]
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Nilutamide Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [5]
NADPH-cytochrome P450 reductase (CPR) DE3N2FM NCPR_HUMAN Metabolism [6]
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Nilutamide Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Response To Substance [7]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [8]
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Indication(s) of Flutamide
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Approved [3]
Flutamide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Androgen receptor (AR) TTS64P2 ANDR_HUMAN Antagonist [9]
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Flutamide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [10]
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Flutamide Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [12]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [13]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [11]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [13]
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⏷ Show the Full List of 6 DME(s)
Flutamide Interacts with 35 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Activity [14]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [8]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [15]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Response To Substance [16]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Response To Substance [16]
3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2) OTTG0NFD S5A2_HUMAN Decreases Activity [17]
Prostate-specific antigen (KLK3) OTFGSBFJ KLK3_HUMAN Decreases Expression [18]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [19]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Increases Expression [20]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [21]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [22]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Increases Expression [23]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [19]
Protein S100-A8 (S100A8) OTVMOB3F S10A8_HUMAN Increases Expression [22]
Protein S100-A9 (S100A9) OTOARHCS S10A9_HUMAN Increases Expression [22]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [21]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [19]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [19]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Decreases Expression [24]
Insulin-like growth factor-binding protein 3 (IGFBP3) OTIX63TX IBP3_HUMAN Decreases Secretion [25]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [26]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Increases Expression [19]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Affects Localization [27]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [19]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Increases Expression [19]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [19]
Advanced glycosylation end product-specific receptor (AGER) OTPY0IH7 RAGE_HUMAN Increases Expression [22]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [19]
Estrogen receptor beta (ESR2) OTXNR2WQ ESR2_HUMAN Increases Expression [23]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) OTZM6MHU NLRP3_HUMAN Increases Expression [22]
Homeobox protein Nkx-3.1 (NKX3-1) OT0DO6ZU NKX31_HUMAN Decreases Expression [28]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [20]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [19]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Affects Response To Substance [29]
Arylacetamide deacetylase (AADAC) OT8VACT2 AAAD_HUMAN Increases Hydrolysis [30]
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⏷ Show the Full List of 35 DOT(s)

References

1 ClinicalTrials.gov (NCT00002855) Chemotherapy Plus Hormone Therapy Versus Androgen Suppression in Treating Patients With Metastatic or Unresectable Prostate Cancer
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: 2864).
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: 6943).
4 CX3CR1 is expressed by prostate epithelial cells and androgens regulate the levels of CX3CL1/fractalkine in the bone marrow: potential role in prostate cancer bone tropism. Cancer Res. 2008 Mar 15;68(6):1715-22.
5 Nilutamide inhibits mephenytoin 4-hydroxylation in untreated male rats and in human liver microsomes. Xenobiotica. 1991 Dec;21(12):1559-70.
6 Generation of free radicals during the reductive metabolism of nilutamide by lung microsomes: possible role in the development of lung lesions in patients treated with this anti-androgen. Biochem Pharmacol. 1992 Feb 4;43(3):654-7.
7 TBECH, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane, alters androgen receptor regulation in response to mutations associated with prostate cancer. Toxicol Appl Pharmacol. 2016 Sep 15;307:91-101. doi: 10.1016/j.taap.2016.07.018. Epub 2016 Jul 27.
8 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
9 Androgen receptor as a target in androgen-independent prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9.
10 The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury. Toxicol Lett. 2003 Apr 30;142(1-2):61-70.
11 Identification of a novel glutathione conjugate of flutamide in incubations with human liver microsomes. Drug Metab Dispos. 2007 Jul;35(7):1081-8.
12 Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997 Nov;25(11):1298-303.
13 Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41.
14 Anti-androgenic effect of 6-formylindolo[3,2-b]carbazole (FICZ) in LNCaP cells is mediated by the aryl hydrocarbon-androgen receptors cross-talk. Steroids. 2020 Jan;153:108508. doi: 10.1016/j.steroids.2019.108508. Epub 2019 Oct 3.
15 Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43.
16 Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury. Arch Toxicol. 2018 Jan;92(1):383-399. doi: 10.1007/s00204-017-2036-4. Epub 2017 Jul 31.
17 Effects of various pesticides on human 5alpha-reductase activity in prostate and LNCaP cells. Toxicol In Vitro. 2007 Apr;21(3):502-8.
18 Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters. Environ Int. 2015 Jan;74:60-70.
19 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
20 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
21 PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line. Cancer Chemother Pharmacol. 2010 Sep;66(4):765-71. doi: 10.1007/s00280-009-1221-4. Epub 2009 Dec 30.
22 Prediction of drug-induced liver injury using keratinocytes. J Appl Toxicol. 2017 Jul;37(7):863-872. doi: 10.1002/jat.3435. Epub 2017 Jan 31.
23 Arylpiperazines for management of benign prostatic hyperplasia: design, synthesis, quantitative structure-activity relationships, and pharmacokinetic studies. J Med Chem. 2011 Jan 13;54(1):302-11. doi: 10.1021/jm101163m. Epub 2010 Dec 3.
24 Role of connexin 43 in cadmium-induced proliferation of human prostate epithelial cells. J Appl Toxicol. 2017 Aug;37(8):933-942. doi: 10.1002/jat.3441. Epub 2017 Feb 8.
25 DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells. Am J Physiol Endocrinol Metab. 2006 May;290(5):E952-60. doi: 10.1152/ajpendo.00451.2005. Epub 2005 Dec 20.
26 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
27 Proliferative and androgenic effects of indirubin derivatives in LNCaP human prostate cancer cells at sub-apoptotic concentrations. Chem Biol Interact. 2011 Feb 1;189(3):177-85. doi: 10.1016/j.cbi.2010.11.008. Epub 2010 Nov 25.
28 Curcumin downregulates homeobox gene NKX3.1 in prostate cancer cell LNCaP. Acta Pharmacol Sin. 2007 Mar;28(3):423-30. doi: 10.1111/j.1745-7254.2007.00501.x.
29 Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation. Drug Metab Dispos. 2011 Aug;39(8):1388-95. doi: 10.1124/dmd.110.037077. Epub 2011 May 3.
30 Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse. Drug Metab Dispos. 2012 Apr;40(4):671-9. doi: 10.1124/dmd.111.043067. Epub 2011 Dec 29.