Details of the Drug Combination

General Information of Drug Combination (ID: DCV70LW)

• Drug Combination Name: Leuprolide + Cetrorelix
• Indication: Polycystic Ovary Syndrome; Status: Phase 4 [1]
• Component Drugs:
  Leuprolide (DM5XPIJ): Small molecular drug
  Cetrorelix (DMFD9Q6): 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	[5]

Leuprolide Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Thyroxine-binding globulin (SERPINA7)	OTUYVTSU	THBG_HUMAN	Increases ADR	[6]
Protein bric-a-brac 2 (bab2)	OTNNK0KI	BAB2_DROME	Increases ADR	[6]

Indication(s) of Cetrorelix

Disease Entry	ICD 11	Status	REF
Ovarian stimulation	LB45.1	Approved	[4]

Cetrorelix 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	[8]

Cetrorelix Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[9]
Tumor necrosis factor ligand superfamily member 13 (TNFSF13)	OT90OWIO	TNF13_HUMAN	Decreases Expression	[7]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[7]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Decreases Expression	[10]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Decreases Expression	[10]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[7]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[7]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[7]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[7]

References

• [1] ClinicalTrials.gov (NCT04094467) Comparison Between Two Different Protocols in Polycystic Ovary Symdrome Women Undergoing Intra-cytoplasmic Injection
• [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: 1190).
• [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] Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo. Mol Cancer Ther. 2011 Jan;10(1):148-58. doi: 10.1158/1535-7163.MCT-10-0829. Epub 2010 Nov 9.
• [8] Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas. Prostate. 2009 Jul 1;69(10):1025-33.
• [9] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [10] Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men. Exp Clin Endocrinol Diabetes. 1999;107(1):63-9. doi: 10.1055/s-0029-1212075.