Details of the Drug Combination

General Information of Drug Combination (ID: DC3IMSZ)

• Drug Combination Name: ABIRATERONE + Uracil mustard
• Indication: High grade ovarian serous adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  ABIRATERONE (DM8V75C): Small molecular drug
  Uracil mustard (DMHL7OB): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: OVCAR-8
  Zero Interaction Potency (ZIP) Score: 12.72
  Bliss Independence Score: 14.03
  Loewe Additivity Score: 5.38
  LHighest Single Agent (HSA) Score: 13.35

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	[5]

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	[6]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[7]
Membrane cofactor protein (CD46)	OTQ8NWJD	MCP_HUMAN	Increases Expression	[8]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Response To Substance	[9]

Indication(s) of Uracil mustard

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[3]
Chronic myelogenous leukaemia	2A20.0	Approved	[4]
Polycythemia vera	2A20.4	Approved	[4]
Small lymphocytic lymphoma	2A82.0	Approved	[4]

Uracil mustard Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[10]

Uracil mustard Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1)	OT7FBG5W	NAR1_HUMAN	Increases ADR	[11]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases ADR	[11]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases ADR	[11]
Poly polymerase 1 (PARP1)	OTIESHK4	PARP1_ARATH	Increases ADR	[11]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases ADR	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCA9LYN	MOLT-4	Investigative	[12]
Astrocytoma	DCYTEU1	SNB-19	Investigative	[12]
Chronic myelogenous leukemia	DCV7CVY	K-562	Investigative	[12]
Clear cell renal cell carcinoma	DC1BUQT	786-0	Investigative	[12]
Clear cell renal cell carcinoma	DC9I1OL	CAKI-1	Investigative	[12]
Glioma	DCNK2AY	SF-295	Investigative	[12]
Plasma cell myeloma	DC60KCI	RPMI-8226	Investigative	[12]
Renal cell carcinoma	DCSMOYD	UO-31	Investigative	[12]
Breast adenocarcinoma	DC3EVNE	MDA-MB-468	Investigative	[13]
Carcinoma	DCAPZRN	MCF7	Investigative	[13]
Colon carcinoma	DCF3SXR	KM12	Investigative	[13]
Adenocarcinoma	DCRFAJW	HCT-15	Investigative	[1]
Adenocarcinoma	DCPOZAB	HCT116	Investigative	[1]
Lung adenocarcinoma	DCI0YQB	NCI-H522	Investigative	[1]
Melanoma	DCJ34B6	SK-MEL-2	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCHRFDT	SK-OV-3	Investigative	[1]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [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] 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: 7621).
• [4] Uracil mustard FDA Label
• [5] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
• [11] 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.
• [12] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [13] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.