Details of the Drug Combination

General Information of Drug Combination (ID: DCNIJI0)

Drug Combination Name
Leuprolide Enzalutamide
Indication
Disease Entry Status REF
Prostate Cancer Phase 2 [1]
Component Drugs Leuprolide   DM5XPIJ Enzalutamide   DMGL19D
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 Leuprolide
Disease Entry ICD 11 Status REF
Plasma cell myeloma 2A83.1 Approved [2]
Prostate cancer 2C82.0 Approved [3]
Endometriosis GA10 Investigative [2]
Leuprolide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Leutinizing-hormone-releasing hormone (GNRH1) TT0ID4A GON1_HUMAN Activator [5]
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Leuprolide Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Thyroxine-binding globulin (SERPINA7) OTUYVTSU THBG_HUMAN Increases ADR [6]
Thyroid peroxidase (TPO) OTJJLL20 PERT_HUMAN Increases ADR [6]
Protein bric-a-brac 2 (bab2) OTNNK0KI BAB2_DROME Increases ADR [6]
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Indication(s) of Enzalutamide
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Approved [4]
Enzalutamide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Androgen receptor (AR) TTS64P2 ANDR_HUMAN Modulator [9]
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Enzalutamide Interacts with 117 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Decreases Response To Substance [10]
Very long chain fatty acid elongase 7 (ELOVL7) OT89NYVC ELOV7_HUMAN Decreases Expression [7]
Bone morphogenetic protein receptor type-1B (BMPR1B) OTGFN0OD BMR1B_HUMAN Decreases Expression [7]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Decreases Expression [7]
RNA polymerase II elongation factor ELL2 (ELL2) OTZJRTFM ELL2_HUMAN Decreases Expression [7]
Suppressor of cytokine signaling 2 (SOCS2) OTBPNKJQ SOCS2_HUMAN Decreases Expression [7]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Decreases Expression [7]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Decreases Expression [7]
Unconventional myosin-Ib (MYO1B) OTGZUJ0I MYO1B_HUMAN Decreases Expression [7]
Kinesin heavy chain isoform 5C (KIF5C) OT35570Y KIF5C_HUMAN Decreases Expression [7]
Transcription factor Maf (MAF) OT1GR3IZ MAF_HUMAN Decreases Expression [7]
Solute carrier family 22 member 3 (SLC22A3) OTQYGVXX S22A3_HUMAN Decreases Expression [7]
Insulin-like growth factor I (IGF1) OTIIZR61 IGF1_HUMAN Decreases Expression [7]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Expression [7]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Expression [7]
Microtubule-associated protein 2 (MAP2) OT6UYT3X MTAP2_HUMAN Decreases Expression [7]
Plastin-2 (LCP1) OTK61F2A PLSL_HUMAN Decreases Expression [7]
Kallikrein-2 (KLK2) OT9RE37R KLK2_HUMAN Decreases Expression [7]
Zinc-alpha-2-glycoprotein (AZGP1) OTPD9TDR ZA2G_HUMAN Decreases Expression [7]
Dipeptidyl peptidase 4 (DPP4) OT16MVL9 DPP4_HUMAN Decreases Expression [7]
Prostaglandin E2 receptor EP4 subtype (PTGER4) OT2GBV06 PE2R4_HUMAN Decreases Expression [7]
Phospholipase A2 group V (PLA2G5) OTQRSKCZ PA2G5_HUMAN Decreases Expression [7]
Regulator of G-protein signaling 2 (RGS2) OT0FSRW7 RGS2_HUMAN Decreases Expression [7]
Retinaldehyde dehydrogenase 3 (ALDH1A3) OT1C9NKQ AL1A3_HUMAN Decreases Expression [7]
Selenoprotein P (SELENOP) OT02B8IR SEPP1_HUMAN Decreases Expression [7]
AF4/FMR2 family member 3 (AFF3) OTR0705Z AFF3_HUMAN Decreases Expression [7]
Cysteine-rich secretory protein 3 (CRISP3) OTBSWMPL CRIS3_HUMAN Decreases Expression [7]
Tumor protein D52 (TPD52) OTPKSK43 TPD52_HUMAN Decreases Expression [7]
Testican-1 (SPOCK1) OTLTDGK7 TICN1_HUMAN Decreases Expression [7]
Acyl-coenzyme A synthetase ACSM1, mitochondrial (ACSM1) OT1TS9M9 ACSM1_HUMAN Decreases Expression [7]
Ras GTPase-activating-like protein IQGAP2 (IQGAP2) OTX2UA7P IQGA2_HUMAN Decreases Expression [7]
Glycine N-methyltransferase (GNMT) OT0O2OQO GNMT_HUMAN Decreases Expression [7]
Ketimine reductase mu-crystallin (CRYM) OTRGSR6B CRYM_HUMAN Decreases Expression [7]
Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase (ADPRM) OTXE3X5J ADPRM_HUMAN Decreases Expression [7]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Decreases Expression [7]
EF-hand calcium-binding domain-containing protein 12 (EFCAB12) OT1QZJEI EFC12_HUMAN Decreases Expression [7]
Rho-related GTP-binding protein RhoU (RHOU) OTERIAD4 RHOU_HUMAN Decreases Expression [7]
Transient receptor potential cation channel subfamily M member 8 (TRPM8) OT7ACGYK TRPM8_HUMAN Decreases Expression [7]
Alpha-protein kinase 2 (ALPK2) OTWZZDQ9 ALPK2_HUMAN Decreases Expression [7]
Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT) OTO68C3Y AADAT_HUMAN Decreases Expression [7]
Chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1) OTBML9D9 CGAT1_HUMAN Decreases Expression [7]
Homeobox protein Nkx-3.1 (NKX3-1) OT0DO6ZU NKX31_HUMAN Decreases Expression [7]
Specifically androgen-regulated gene protein (C1ORF116) OTPYEXDM SARG_HUMAN Decreases Expression [7]
ER degradation-enhancing alpha-mannosidase-like protein 3 (EDEM3) OT4GJX9R EDEM3_HUMAN Decreases Expression [7]
Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 1 (ST6GALNAC1) OT3JQD99 SIA7A_HUMAN Decreases Expression [7]
Teneurin-1 (TENM1) OTSKSU4V TEN1_HUMAN Decreases Expression [7]
Transmembrane and coiled-coil domain protein 3 (TMCC3) OTAIQ6V6 TMCC3_HUMAN Decreases Expression [7]
E3 ubiquitin-protein ligase NEURL1B (NEURL1B) OT3BZWO8 NEU1B_HUMAN Affects Expression [8]
Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) OTOKUXUH ADA10_HUMAN Affects Expression [8]
Integrin beta-1-binding protein 1 (ITGB1BP1) OTVQFNGS ITBP1_HUMAN Affects Expression [8]
Sushi domain-containing protein 5 (SUSD5) OTIMJGDH SUSD5_HUMAN Affects Expression [8]
GDP-mannose 4,6 dehydratase (GMDS) OTWV79YD GMDS_HUMAN Affects Expression [8]
Polycomb protein EED (EED) OTJFHCDF EED_HUMAN Decreases Expression [11]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [12]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Affects Expression [8]
Prostate-specific antigen (KLK3) OTFGSBFJ KLK3_HUMAN Decreases Expression [12]
Beta-microseminoprotein (MSMB) OTYORAJC MSMB_HUMAN Decreases Expression [13]
Keratin, type I cytoskeletal 19 (KRT19) OTDGDQ75 K1C19_HUMAN Affects Expression [8]
Annexin A4 (ANXA4) OTUCRYXL ANXA4_HUMAN Affects Expression [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Cleavage [12]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [11]
Membrane cofactor protein (CD46) OTQ8NWJD MCP_HUMAN Increases Expression [14]
Aspartate aminotransferase, cytoplasmic (GOT1) OTZLM5UB AATC_HUMAN Affects Expression [8]
Midkine (MDK) OTF24HKC MK_HUMAN Affects Expression [8]
Hepatocyte nuclear factor 1-beta (HNF1B) OTSYIC3T HNF1B_HUMAN Affects Expression [8]
Small ribosomal subunit protein eS19 (RPS19) OTBKGP48 RS19_HUMAN Affects Expression [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Affects Expression [8]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Affects Expression [8]
Transcription factor SOX-9 (SOX9) OTVDJFGN SOX9_HUMAN Affects Expression [8]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Affects Expression [8]
Presenilin-1 (PSEN1) OTKL39RT PSN1_HUMAN Affects Expression [8]
Presenilin-2 (PSEN2) OTOW778B PSN2_HUMAN Affects Expression [8]
Hepatocyte nuclear factor 3-alpha (FOXA1) OTEBY0TD FOXA1_HUMAN Affects Expression [8]
Ubiquitin-ribosomal protein eS31 fusion protein (RPS27A) OTIIGGZ2 RS27A_HUMAN Affects Expression [8]
Protein jagged-1 (JAG1) OT3LGT6K JAG1_HUMAN Affects Expression [8]
Disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) OTTM6KRB ADA17_HUMAN Affects Expression [8]
Neurogenic locus notch homolog protein 2 (NOTCH2) OTQ3Y9PA NOTC2_HUMAN Affects Expression [8]
Recombining binding protein suppressor of hairless (RBPJ) OTD7CUG0 SUH_HUMAN Affects Expression [8]
Histone acetyltransferase p300 (EP300) OTL8QJDX EP300_HUMAN Affects Expression [8]
Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5) OT404F9K FKBP5_HUMAN Decreases Expression [12]
SNW domain-containing protein 1 (SNW1) OTKWG3PS SNW1_HUMAN Affects Expression [8]
Transcription factor HES-1 (HES1) OT8P19W2 HES1_HUMAN Affects Expression [8]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Decreases Expression [11]
Polycomb protein SUZ12 (SUZ12) OT655XF8 SUZ12_HUMAN Decreases Expression [11]
Histone-lysine N-methyltransferase EZH2 (EZH2) OTIEHTKW EZH2_HUMAN Decreases Expression [11]
Probable E3 ubiquitin-protein ligase DTX2 (DTX2) OT7QLDU4 DTX2_HUMAN Affects Expression [8]
E3 ubiquitin-protein ligase MIB1 (MIB1) OT5C404P MIB1_HUMAN Affects Expression [8]
NF-kappa-B-activating protein (NKAP) OT7K7I8Q NKAP_HUMAN Affects Expression [8]
Probable E3 ubiquitin-protein ligase DTX3 (DTX3) OTSUUV9N DTX3_HUMAN Affects Expression [8]
Polypeptide N-acetylgalactosaminyltransferase 11 (GALNT11) OTANT9E6 GLT11_HUMAN Affects Expression [8]
Gamma-secretase subunit APH-1B (APH1B) OTQHPTGC APH1B_HUMAN Affects Expression [8]
Nicastrin (NCSTN) OT5QBTA4 NICA_HUMAN Affects Expression [8]
Mastermind-like protein 1 (MAML1) OTQA4DDN MAML1_HUMAN Affects Expression [8]
CREB-binding protein (CREBBP) OTPA4QGM CBP_HUMAN Affects Expression [8]
Histone acetyltransferase KAT2B (KAT2B) OTWQITWK KAT2B_HUMAN Affects Expression [8]
E3 ubiquitin-protein ligase MIB2 (MIB2) OTJCC3HS MIB2_HUMAN Affects Expression [8]
Gamma-secretase subunit APH-1A (APH1A) OT97F1TU APH1A_HUMAN Affects Expression [8]
p53 apoptosis effector related to PMP-22 (PERP) OTP0YL53 PERP_HUMAN Affects Expression [8]
E3 ubiquitin-protein ligase Itchy homolog (ITCH) OTUOMKF5 ITCH_HUMAN Affects Expression [8]
Mastermind-like protein 3 (MAML3) OTZFV53Z MAML3_HUMAN Affects Expression [8]
Intraflagellar transport protein 74 homolog (IFT74) OTZBFEDD IFT74_HUMAN Affects Expression [8]
RNA-binding protein 15 (RBM15) OT8ZPGWF RBM15_HUMAN Affects Expression [8]
Msx2-interacting protein (SPEN) OT37A2MD MINT_HUMAN Affects Expression [8]
Sphingosine 1-phosphate receptor 3 (S1PR3) OTXBIYO8 S1PR3_HUMAN Affects Expression [8]
GDP-fucose protein O-fucosyltransferase 1 (POFUT1) OTOBJZIT OFUT1_HUMAN Affects Expression [8]
Notchless protein homolog 1 (NLE1) OT1BV82K NLE1_HUMAN Affects Expression [8]
Gamma-secretase subunit PEN-2 (PSENEN) OTJ7M7G9 PEN2_HUMAN Affects Expression [8]
Protein sel-1 homolog 1 (SEL1L) OTC0FB7T SE1L1_HUMAN Affects Expression [8]
Intraflagellar transport protein 172 homolog (IFT172) OT12DW08 IF172_HUMAN Affects Expression [8]
Neurogenic locus notch homolog protein 3 (NOTCH3) OTMVVA7F NOTC3_HUMAN Affects Expression [8]
Protein jagged-2 (JAG2) OTH7KRRF JAG2_HUMAN Affects Expression [8]
E3 ubiquitin-protein ligase DTX4 (DTX4) OTGX30AO DTX4_HUMAN Affects Expression [8]
Epsin-1 (EPN1) OT4Q1NIV EPN1_HUMAN Affects Expression [8]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Response To Substance [15]
Ephrin type-B receptor 4 (EPHB4) OTKLPVXJ EPHB4_HUMAN Affects Response To Substance [12]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Response To Substance [15]
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⏷ Show the Full List of 117 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hormone Sensitive Prostate Cancer DCPV5K3 N. A. Phase 3 [16]
Prostate Cancer DCZAT12 N. A. Phase 2 [17]
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References

1 ClinicalTrials.gov (NCT02064582) Enzalutamide and Hormone Therapy Before, During, and After Radiation for High Risk Localized Prostate Cancer
2 Leuprolide FDA Label
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: 1175).
4 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
5 Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer. Pharmacotherapy. 2008 Dec;28(12):1511-22.
6 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.
7 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
8 NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
10 Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015 Jul 13;43(12):5880-97. doi: 10.1093/nar/gkv262. Epub 2015 Apr 23.
11 Dual targeting of EZH2 and androgen receptor as a novel therapy for castration-resistant prostate cancer. Toxicol Appl Pharmacol. 2020 Oct 1;404:115200. doi: 10.1016/j.taap.2020.115200. Epub 2020 Aug 14.
12 Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance. J Biol Chem. 2020 Apr 17;295(16):5470-5483. doi: 10.1074/jbc.RA119.011385. Epub 2020 Mar 17.
13 In silico and in vitro assessment of androgen receptor antagonists. Comput Biol Chem. 2021 Jun;92:107490. doi: 10.1016/j.compbiolchem.2021.107490. Epub 2021 Apr 23.
14 Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer. JCI Insight. 2018 Sep 6;3(17):e121497. doi: 10.1172/jci.insight.121497. eCollection 2018 Sep 6.
15 Niclosamide suppresses cell migration and invasion in enzalutamide resistant prostate cancer cells via Stat3-AR axis inhibition. Prostate. 2015 Sep;75(13):1341-53. doi: 10.1002/pros.23015. Epub 2015 May 13.
16 ClinicalTrials.gov (NCT02319837) Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)
17 ClinicalTrials.gov (NCT01547299) Study of Enzalutamide (Formerly MDV3100) as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer