Details of the Drug Combination

General Information of Drug Combination (ID: DCHLJ9E)

• Drug Combination Name: ABIRATERONE + ONAPRISTONE
• Indication: Prostate Cancer; Status: Phase 1 [1]
• Component Drugs:
  ABIRATERONE (DM8V75C): Small molecular drug
  ONAPRISTONE (DMT6E5N): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of ABIRATERONE

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

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	[4]

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	[5]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[6]
Membrane cofactor protein (CD46)	OTQ8NWJD	MCP_HUMAN	Increases Expression	[7]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Response To Substance	[8]

Indication(s) of ONAPRISTONE

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[3]

ONAPRISTONE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Modulator	[9]

ONAPRISTONE Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]

ONAPRISTONE Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Affects Binding	[11]

References

• [1] ClinicalTrials.gov (NCT02049190) Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer
• [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: 6745).
• [3] Clinical pipeline report, company report or official report of Context Therapeutics.
• [4] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer. Eur J Cancer. 1999 Feb;35(2):214-8.
• [10] Drug-metabolizing enzymes and transporters: expression in the human prostate and roles in prostate drug disposition. J Androl. 2006 Mar-Apr;27(2):138-50.
• [11] Ligand-selective targeting of the glucocorticoid receptor to nuclear subdomains is associated with decreased receptor mobility. Mol Endocrinol. 2005 Jun;19(6):1501-15. doi: 10.1210/me.2005-0050. Epub 2005 Feb 10.