Details of the Drug Combination

General Information of Drug Combination (ID: DCZXJZA)

• Drug Combination Name: Leuprolide + Goserelin
• Indication: Breast Cancer; Status: Phase 3 [1]
• Component Drugs:
  Leuprolide (DM5XPIJ): Small molecular drug
  Goserelin (DMAT8CG): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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	[6]

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	[7]
Thyroid peroxidase (TPO)	OTJJLL20	PERT_HUMAN	Increases ADR	[7]
Protein bric-a-brac 2 (bab2)	OTNNK0KI	BAB2_DROME	Increases ADR	[7]

Indication(s) of Goserelin

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[4]
Estrogen-receptor positive breast cancer	N.A.	Approved	[5]
Endometriosis	GA10	Investigative	[5]
Male breast carcinoma	N.A.	Investigative	[5]

Goserelin 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	[8]

Goserelin Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Decreases Expression	[9]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Expression	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[10]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[10]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Secretion	[11]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Prostate Cancer	DC763GJ	N. A.	Phase 3	[12]
Prostate Cancer	DC9C9SC	N. A.	Phase 3	[13]
Gastrointestinal Complications	DCW1ETX	N. A.	Phase 3	[14]
Breast Cancer	DCY45M7	N. A.	Phase 2	[15]
Adenocarcinoma of the Prostate	DC43XRL	N. A.	Phase 2	[16]
Recurrent Prostate Cancer	DCLI0V7	N. A.	Phase 2	[17]
Prostate Cancer	DCVMLM2	N. A.	Phase 2	[18]
Prostate Cancer	DCHVXZQ	N. A.	Phase 1	[19]
Recurrent Prostate Cancer	DC6Z3D7	N. A.	Phase 1	[20]
Prostate Cancer	DCTGJYL	N. A.	Phase 1	[21]
Adenocarcinoma of the Prostate	DCD7XMI	N. A.	Phase 1	[22]

References

• [1] ClinicalTrials.gov (NCT02941926) Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBC
• [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] 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: 3879).
• [5] Goserelin FDA Label
• [6] 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.
• [7] 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.
• [8] Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):341-9.
• [9] [Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment of moderate-severe endometriosis: a clinical observation]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1288-91.
• [10] A comparative study of the effect of raloxifene and gosereline on uterine leiomyoma volume changes and estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically in premenopausal women. Eur J Obstet Gynecol Reprod Biol. 2007 Nov;135(1):94-103. doi: 10.1016/j.ejogrb.2006.07.042. Epub 2006 Sep 14.
• [11] Prostate specific antigen expression does not necessarily correlate with prostate cancer cell growth. J Urol. 2006 Jul;176(1):354-60. doi: 10.1016/S0022-5347(06)00516-7.
• [12] ClinicalTrials.gov (NCT00388804) External Beam Radiation Therapy (EBRT) With or Without Hormonal Therapy in Prostate Cancer
• [13] ClinicalTrials.gov (NCT00002597) Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer
• [14] ClinicalTrials.gov (NCT00541047) RADICALS - Radiotherapy and Androgen Deprivation In Combination After Local Surgery
• [15] ClinicalTrials.gov (NCT03056755) Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments
• [16] ClinicalTrials.gov (NCT02058706) LHRH Analogue Therapy With Enzalutamide or Bicalutamide in Treating Patients With Hormone Sensitive Prostate Cancer
• [17] ClinicalTrials.gov (NCT01750398) Bipolar Androgen-based Therapy for Prostate Cancer (BAT)
• [18] ClinicalTrials.gov (NCT02059213) A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer
• [19] ClinicalTrials.gov (NCT02366494) Micro RNAs to Predict Response to Androgen Deprivation Therapy
• [20] ClinicalTrials.gov (NCT00454571) Pazopanib Hydrochloride After Leuprolide Acetate or Goserelin Acetate in Treating Patients With Relapsed Prostate Cancer
• [21] ClinicalTrials.gov (NCT00004635) Thalidomide for the Treatment of Hormone-Dependent Prostate Cancer
• [22] ClinicalTrials.gov (NCT02023463) Enzalutamide, Radiation Therapy and Hormone Therapy in Treating Patients With Intermediate or High-Risk Prostate Cancer