Details of the Drug Combination

General Information of Drug Combination (ID: DCWFB6E)

• Drug Combination Name: Leuprolide + ABIRATERONE
• Indication: Newly Diagnosed Oligometastatic Prostate Cancer; Status: Phase 2 [1]
• Component Drugs:
  Leuprolide (DM5XPIJ): Small molecular drug
  ABIRATERONE (DM8V75C): 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 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]

Indication(s) of ABIRATERONE

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[4]

ABIRATERONE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-monooxygenase (S17AH)	TTRA5BZ	CP17A_HUMAN	Modulator	[7]

ABIRATERONE Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Activity	[8]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[9]
Membrane cofactor protein (CD46)	OTQ8NWJD	MCP_HUMAN	Increases Expression	[10]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Response To Substance	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Prostate Cancer	DCLJJZL	N. A.	Phase 2	[12]
Prostate Cancer	DCHM8XH	N. A.	Phase 2	[13]
Prostate Cancer	DCC5P8T	N. A.	Phase 1	[14]

References

• [1] ClinicalTrials.gov (NCT03298087) Systemic and Tumor-Directed Therapy for Oligometastatic 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] 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: 6745).
• [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] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [8] A fission yeast-based test system for the determination of IC50 values of anti-prostate tumor drugs acting on CYP21. J Enzyme Inhib Med Chem. 2006 Oct;21(5):547-56.
• [9] Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
• [10] 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.
• [11] 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.
• [12] ClinicalTrials.gov (NCT03043807) A Study of Definitive Therapy to Treat Prostate Cancer After Prostatectomy
• [13] ClinicalTrials.gov (NCT02772588) AASUR in High Risk Prostate Cancer
• [14] ClinicalTrials.gov (NCT04194554) A Multi-Center Trial of Androgen Suppression With Abiraterone Acetate, Leuprolide, PARP Inhibition and Stereotactic Body Radiotherapy in Prostate Cancer