Details of the Drug Combination

General Information of Drug Combination (ID: DC2MNA6)

Drug Combination Name

Goserelin Dutasteride

Indication

Disease Entry	Status	REF
Salivary Duct Carcinoma	Phase 2	[1]

Component Drugs

Goserelin DMAT8CG

Dutasteride DMQ4TJK

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Goserelin

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Estrogen-receptor positive breast cancer	N.A.	Approved	[3]
Endometriosis	GA10	Investigative	[3]
Male breast carcinoma	N.A.	Investigative	[3]

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	[6]
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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	[7]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Expression	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[8]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[8]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Secretion	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[8]
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⏷ Show the Full List of 6 DOT(s)

Indication(s) of Dutasteride

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[4]
Prostate adenocarcinoma	N.A.	Approved	[5]
Prostate cancer	2C82.0	Phase 3	[4]

Dutasteride Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Oxo-5-alpha-steroid 4-dehydrogenase (SRD5A)	TT2A0DR	S5A1_HUMAN; S5A2_HUMAN; PORED_HUMAN	Inhibitor	[11]
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Dutasteride Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]
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Dutasteride Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1)	OTQRET2B	S5A1_HUMAN	Decreases Expression	[14]
3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2)	OTTG0NFD	S5A2_HUMAN	Decreases Expression	[14]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Increases Expression	[14]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Increases Expression	[14]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Increases Expression	[14]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Expression	[10]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Expression	[10]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Expression	[10]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)	OT6EBDHM	DHB1_HUMAN	Increases Expression	[10]
Cytochrome P450 11B2, mitochondrial (CYP11B2)	OTIOLWYN	C11B2_HUMAN	Increases Expression	[10]
Kallikrein-2 (KLK2)	OT9RE37R	KLK2_HUMAN	Decreases Expression	[10]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Increases Expression	[10]
17-beta-hydroxysteroid dehydrogenase type 3 (HSD17B3)	OT45D396	DHB3_HUMAN	Increases Expression	[10]
Son of sevenless homolog 1 (SOS1)	OTTCWXC3	SOS1_HUMAN	Increases Expression	[10]
Delta(24)-sterol reductase (DHCR24)	OTP301JW	DHC24_HUMAN	Decreases Expression	[10]
Calreticulin (CALR)	OTYD2TR1	CALR_HUMAN	Decreases Expression	[15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[16]
ELL-associated factor 2 (EAF2)	OTSOET5L	EAF2_HUMAN	Decreases Expression	[15]
Acireductone dioxygenase (ADI1)	OT8IOD03	MTND_HUMAN	Decreases Expression	[15]
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⏷ Show the Full List of 19 DOT(s)

References

1	ClinicalTrials.gov (NCT05513365) Phase II Dutasteride in Combination With CAB vs CAB in SDC
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: 3879).
3	Goserelin FDA Label
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: 7457).
5	Dutasteride FDA Label
6	Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):341-9.
7	[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.
8	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.
9	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.
10	Effects of dutasteride on the expression of genes related to androgen metabolism and related pathway in human prostate cancer cell lines. Invest New Drugs. 2007 Oct;25(5):491-7.
11	The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S109-14.
12	Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94.
13	Product monograph: Avodart (dutasteride capsules).
14	Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):129-40.
15	Inhibition of 5alpha-reductase enhances testosterone-induced expression of U19/Eaf2 tumor suppressor during the regrowth of LNCaP xenograft tumor in nude mice. Prostate. 2010 Oct 1;70(14):1575-85. doi: 10.1002/pros.21193.
16	Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.