Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM5XPIJ)

• Drug Name: Leuprolide Drug Info
• Synonyms: Enantone; Eligard (TN); Leuprorelin (INN); Viadur (TN); 5-oxoprolylhistidyltryptophylseryltyrosylleucylleucyl-n5-(diaminomethylidene)ornithyl-n-ethylprolinamide

Indication

Disease Entry	ICD 11	Status	REF
Plasma cell myeloma	2A83.1	Approved	[1]
Prostate cancer	2C82.0	Approved	[2]
Endometriosis	GA10	Investigative	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 657181
  ChEBI ID: CHEBI:6427
  CAS Number: CAS 53714-56-0
  TTD Drug ID: DM5XPIJ

Molecule-Related Drug Atlas

Drug(s) Targeting Leutinizing-hormone-releasing hormone (GNRH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Goserelin	DMAT8CG	Breast cancer	2C60-2C65	Approved	[5]
NAL-GLU	DMD5AEB	Prostate cancer	2C82.0	Phase 2/3	[6]
CG201	DMWY609	Solid tumour/cancer	2A00-2F9Z	Phase 2	[7]
Norelin	DMYCLZR	Prostate cancer	2C82.0	Discontinued in Phase 2	[8]
TAK-810	DMCFOSG	Prostate cancer	2C82.0	Discontinued in Phase 1	[9]
Anti-GnRH Spiegelmer	DM4HKC8	Discovery agent	N.A.	Investigative	[10]

Drug(s) Affected By Thyroxine-binding globulin (SERPINA7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[11]
Liothyronine	DM6IR3P	Congenital hypothyroidism		Approved	[12]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[13]
Lindane	DMB8CNL	Infestations of lice and scabies	1G00.Z	Approved	[14]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[15]
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[16]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[13]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[19]

Drug(s) Affected By Thyroid peroxidase (TPO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[20]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[21]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[22]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Propylthiouracil	DM6D7N8	Hyperthyroidism	5A02	Approved	[24]
Nevirapine	DM6HX9B	Human immunodeficiency virus infection	1C62	Approved	[25]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[26]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[23]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[27]
Efavirenz	DMC0GSJ	Human immunodeficiency virus infection	1C62	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Leutinizing-hormone-releasing hormone (GNRH1)	TT0ID4A	GON1_HUMAN	Activator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Protein bric-a-brac 2 (bab2)	OTNNK0KI	BAB2_DROME	Drug Response	[4]
Thyroid peroxidase (TPO)	OTJJLL20	PERT_HUMAN	Drug Response	[4]
Thyroxine-binding globulin (SERPINA7)	OTUYVTSU	THBG_HUMAN	Drug Response	[4]

References

• [1] Leuprolide FDA Label
• [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: 1175).
• [3] 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.
• [4] 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.
• [5] Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):341-9.
• [6] The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women. Am J Obstet Gynecol. 1991 Dec;165(6Pt 1):1811-7.
• [7] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [8] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011623)
• [9] EP patent application no. 2018865, Combination comprising n-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[1,3,4-oxadiazol-2-yl]phenyl)pyridine-3-sulphonamide and an lhrh analogue and/or a bisphosphonate.
• [10] In vivo properties of an anti-GnRH Spiegelmer: an example of an oligonucleotide-based therapeutic substance class. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8898-902.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins. Toxicology. 2010 Nov 9;277(1-3):20-8. doi: 10.1016/j.tox.2010.08.012. Epub 2010 Sep 8.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit adults. Environ Health Perspect. 2009 Sep;117(9):1380-6. doi: 10.1289/ehp.0900633. Epub 2009 May 12.
• [15] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [19] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [20] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [21] Identification of classifiers for increase or decrease of thyroid peroxidase activity in the FTC-238/hTPO recombinant cell line. Environ Sci Technol. 2011 Sep 15;45(18):7906-14. doi: 10.1021/es200475k. Epub 2011 Aug 24.
• [22] The comparative effects of gene modulators on thyroid-specific genes and radioiodine uptake. Cancer Biother Radiopharm. 2007 Jun;22(3):443-9. doi: 10.1089/cbr.2006.319.A.
• [23] Arsenic trioxide and reduced glutathione act synergistically to augment inhibition of thyroid peroxidase activity in vitro. Biol Trace Elem Res. 2015 May;165(1):110-7. doi: 10.1007/s12011-015-0230-x. Epub 2015 Jan 17.
• [24] Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways. Toxicol Appl Pharmacol. 2012 Apr 1;260(1):81-8. doi: 10.1016/j.taap.2012.01.029. Epub 2012 Feb 8.
• [25] Reverse transcriptase inhibitors down-regulate cell proliferation in vitro and in vivo and restore thyrotropin signaling and iodine uptake in human thyroid anaplastic carcinoma. J Clin Endocrinol Metab. 2005 Oct;90(10):5663-71. doi: 10.1210/jc.2005-0367. Epub 2005 Jul 19.
• [26] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [27] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.