General Information of Drug Combination (ID: DCEVAMU)

Drug Combination Name
Relugolix Ritonavir
Indication
Disease Entry Status REF
Prostate Cancer Phase 1 [1]
Component Drugs Relugolix   DMK7IWL Ritonavir   DMU764S
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 Relugolix
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Approved [2]
Endometriosis GA10 Phase 3 [3]
Relugolix Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Gonadotropin-releasing hormone receptor (GNRHR) TT8R70G GNRHR_HUMAN Antagonist [2]
------------------------------------------------------------------------------------
Relugolix Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]
------------------------------------------------------------------------------------
Indication(s) of Ritonavir
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [4]
Ritonavir Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human immunodeficiency virus Protease (HIV PR) TT5FNQT POL_HV1B1 Inhibitor [8]
------------------------------------------------------------------------------------
Ritonavir Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [9]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [11]
------------------------------------------------------------------------------------
Ritonavir Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [13]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [14]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [12]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [15]
------------------------------------------------------------------------------------
Ritonavir Interacts with 90 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Decreases Activity [16]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Activity [17]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [18]
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Decreases Expression [19]
Sterol regulatory element-binding protein 2 (SREBF2) OTBXUNPL SRBP2_HUMAN Increases ADR [20]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Increases ADR [20]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [21]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Expression [21]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Expression [21]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Expression [21]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [22]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [23]
Fibroblast growth factor 19 (FGF19) OT2DVJWY FGF19_HUMAN Increases Expression [17]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Decreases Expression [17]
Growth-regulated alpha protein (CXCL1) OT3WCTZV GROA_HUMAN Decreases Expression [17]
Interleukin-7 (IL7) OTT6YSKM IL7_HUMAN Decreases Expression [17]
C-C motif chemokine 4 (CCL4) OT6B8P25 CCL4_HUMAN Decreases Expression [17]
Leukemia inhibitory factor (LIF) OTO46S5S LIF_HUMAN Decreases Expression [17]
C-X-C motif chemokine 2 (CXCL2) OTEJCYMY CXCL2_HUMAN Decreases Expression [17]
Sterol carrier protein 2 (SCP2) OTPAFCPQ SCP2_HUMAN Decreases Expression [17]
Cytochrome P450 7A1 (CYP7A1) OT8Z5KLD CP7A1_HUMAN Decreases Expression [17]
Interleukin-32 (IL32) OT3FHZ81 IL32_HUMAN Decreases Expression [17]
MHC class II transactivator (CIITA) OTRJNZFO C2TA_HUMAN Increases Expression [17]
C-X-C motif chemokine 5 (CXCL5) OTZOUPCA CXCL5_HUMAN Decreases Expression [17]
Stromal cell-derived factor 1 (CXCL12) OT2QX5LL SDF1_HUMAN Decreases Expression [17]
C-C motif chemokine 20 (CCL20) OTUCJY4N CCL20_HUMAN Decreases Expression [17]
C-X-C motif chemokine 6 (CXCL6) OTFTCQ4O CXCL6_HUMAN Decreases Expression [17]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Expression [17]
Organic solute transporter subunit alpha (SLC51A) OTDJRZ0P OSTA_HUMAN Decreases Expression [17]
Protein NLRC5 (NLRC5) OTY8X6MC NLRC5_HUMAN Decreases Expression [17]
Heat shock protein 105 kDa (HSPH1) OTVRR73T HS105_HUMAN Increases Expression [17]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Increases Expression [17]
7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase (CYP8B1) OTRI4UR1 CP8B1_HUMAN Decreases Expression [17]
Transcription factor E2F3 (E2F3) OT5VQMWY E2F3_HUMAN Decreases Expression [24]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [25]
G1/S-specific cyclin-E2 (CCNE2) OTBBUKQQ CCNE2_HUMAN Decreases Expression [24]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [26]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [25]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [27]
Prelamin-A/C (LMNA) OT3SG7ZR LMNA_HUMAN Increases Expression [28]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [29]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [30]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [24]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [19]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Increases Expression [31]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [26]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Increases Expression [24]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [26]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [24]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [28]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Increases Expression [19]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [24]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [24]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Phosphorylation [32]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [19]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [24]
Beta-galactosidase (GLB1) OTB0TKAG BGAL_HUMAN Increases Activity [28]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Activity [25]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [24]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [33]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [30]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Expression [24]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Phosphorylation [25]
Retinoblastoma-like protein 1 (RBL1) OTDEBFYC RBL1_HUMAN Increases Expression [24]
Caspase-1 (CASP1) OTZ3YQFU CASP1_HUMAN Decreases Expression [27]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Decreases Expression [34]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [25]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Increases Expression [35]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [24]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Phosphorylation [32]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Decreases Expression [19]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Activity [27]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B) OTAG24N1 CDN2B_HUMAN Increases Expression [24]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [24]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Decreases Expression [27]
Cyclin-dependent kinase 3 (CDK3) OT2GP6RL CDK3_HUMAN Increases Expression [24]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [24]
Cyclin-dependent kinase 5 (CDK5) OT1YAK9F CDK5_HUMAN Decreases Expression [24]
Transcription factor E2F1 (E2F1) OTLKYBBC E2F1_HUMAN Decreases Expression [24]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Activity [25]
Proto-oncogene c-Rel (REL) OTTCKMAC REL_HUMAN Decreases Activity [25]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [25]
Retinoblastoma-like protein 2 (RBL2) OTBQSOE6 RBL2_HUMAN Decreases Expression [24]
Transcription factor E2F2 (E2F2) OTO75RM7 E2F2_HUMAN Decreases Expression [24]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [31]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [24]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [36]
Scavenger receptor class B member 1 (SCARB1) OTAE1UA1 SCRB1_HUMAN Increases Expression [35]
AP-2 complex subunit alpha-2 (AP2A2) OTD1UGUN AP2A2_HUMAN Increases ADR [20]
Lipoprotein lipase (LPL) OTTW0267 LIPL_HUMAN Increases ADR [20]
------------------------------------------------------------------------------------
⏷ Show the Full List of 90 DOT(s)

References

1 ClinicalTrials.gov (NCT05679388) A Study of Extending Relugolix Dosing Intervals Through Addition of Itraconazole or Ritonavir in Prostate Cancer Patients
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
5 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
6 A potent HIV protease inhibitor, darunavir, does not inhibit ZMPSTE24 or lead to an accumulation of farnesyl-prelamin A in cells. J Biol Chem. 2008 Apr 11;283(15):9797-804. doi: 10.1074/jbc.M709629200. Epub 2008 Jan 28.
7 Modulation of UDP-glucuronosyltransferase 1A1 in primary human hepatocytes by prototypical inducers. J Biochem Mol Toxicol. 2005;19(2):96-108. doi: 10.1002/jbt.20058.
8 Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr;33(4):307-20.
9 Interaction of eight HIV protease inhibitors with the canalicular efflux transporter ABCC2 (MRP2) in sandwich-cultured rat and human hepatocytes. Biopharm Drug Dispos. 2010 Mar;31(2-3):178-88.
10 MDR1 G1199A polymorphism alters permeability of HIV protease inhibitors across P-glycoprotein-expressing epithelial cells. AIDS. 2005 Oct 14;19(15):1617-25.
11 pH dependence of organic anion-transporting polypeptide 2B1 in Caco-2 cells: potential role in antiretroviral drug oral bioavailability and drug-drug interactions. J Pharmacol Exp Ther. 2010 Sep 1;334(3):1009-22.
12 Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir. Clin Pharmacol Ther. 2006 Mar;79(3):243-54.
13 Reversible coma caused by risperidone-ritonavir interaction. Clin Neuropharmacol. 2002 Sep-Oct;25(5):251-3.
14 Drug Interactions Flockhart Table
15 Evaluation of CYP2B6 induction and prediction of clinical drug-drug interactions: considerations from the IQ consortium induction working group-an industry perspective. Drug Metab Dispos. 2016 Oct;44(10):1720-30.
16 Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
17 Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes. Chem Biol Interact. 2016 Aug 5;255:31-44.
18 Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
19 Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages. Antivir Ther. 2007;12(4):489-500.
20 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.
21 Severe interaction between ritonavir and acenocoumarol. Ann Pharmacother. 2002 Apr;36(4):621-3.
22 Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78.
23 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
24 Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells. Mol Cancer. 2009 Apr 22;8:26. doi: 10.1186/1476-4598-8-26.
25 Efficient intervention of growth and infiltration of primary adult T-cell leukemia cells by an HIV protease inhibitor, ritonavir. Blood. 2006 Jan 15;107(2):716-24. doi: 10.1182/blood-2005-02-0735. Epub 2005 Sep 20.
26 The HIV protease inhibitor ritonavir synergizes with butyrate for induction of apoptotic cell death and mediates expression of heme oxygenase-1 in DLD-1 colon carcinoma cells. Br J Pharmacol. 2004 Dec;143(7):890-8. doi: 10.1038/sj.bjp.0706023. Epub 2004 Oct 25.
27 HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells. J Hum Virol. 1999 Sep-Oct;2(5):261-9.
28 Premature senescence of vascular cells is induced by HIV protease inhibitors: implication of prelamin A and reversion by statin. Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2611-20. doi: 10.1161/ATVBAHA.110.213603. Epub 2010 Sep 30.
29 Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
30 Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer. Clin Cancer Res. 2006 Mar 15;12(6):1883-96. doi: 10.1158/1078-0432.CCR-05-1167.
31 Heme oxygenase-1-derived bilirubin counteracts HIV protease inhibitor-mediated endothelial cell dysfunction. Free Radic Biol Med. 2016 May;94:218-29. doi: 10.1016/j.freeradbiomed.2016.03.003. Epub 2016 Mar 8.
32 The human immunodeficiency virus protease inhibitor ritonavir inhibits lung cancer cells, in part, by inhibition of survivin. J Thorac Oncol. 2011 Apr;6(4):661-70. doi: 10.1097/JTO.0b013e31820c9e3c.
33 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.
34 Nordihydroguaiaretic acid (NDGA) inhibits ritonavir-induced endothelial dysfunction in porcine pulmonary arteries. Med Sci Monit. 2011 Nov;17(11):BR312-318. doi: 10.12659/msm.882040.
35 Estrogen prevents cholesteryl ester accumulation in macrophages induced by the HIV protease inhibitor ritonavir. J Cell Biochem. 2008 Apr 1;103(5):1598-606. doi: 10.1002/jcb.21546.
36 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.