Details of the Drug Combination

General Information of Drug Combination (ID: DCMI4OD)

Drug Combination Name

Amonafide Uracil mustard

Indication

Disease Entry	Status	REF
Clear cell renal cell carcinoma	Investigative	[1]

Component Drugs

Amonafide DMAH59S

Uracil mustard DMHL7OB

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: 786-0

Zero Interaction Potency (ZIP) Score: 1.26

Bliss Independence Score: 5.26

Loewe Additivity Score: 0.42

LHighest Single Agent (HSA) Score: 7.18

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Amonafide

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[2]
Ovarian cancer	2C73	Phase 3	[2]
Prostate cancer	2C82.0	Phase 3	[2]

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	[5]
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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	[6]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases ADR	[6]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases ADR	[6]
Poly polymerase 1 (PARP1)	OTIESHK4	PARP1_ARATH	Increases ADR	[6]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases ADR	[6]
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Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC6SA21	OVCAR3	Investigative	[1]
Adult acute myeloid leukemia	DCUF41O	HL-60(TB)	Investigative	[1]
Anaplastic large cell lymphoma	DC8LWD8	SR	Investigative	[1]
Astrocytoma	DCVUYYC	SNB-19	Investigative	[1]
Clear cell renal cell carcinoma	DCHB574	CAKI-1	Investigative	[1]
Glioblastoma	DCM681M	SNB-75	Investigative	[1]
Glioma	DCDOFHS	SF-268	Investigative	[1]
Glioma	DCG8T8J	SF-295	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCHY6KH	OVCAR-4	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCS32UT	NCI\\/ADR-RES	Investigative	[1]
Large cell lung carcinoma	DCMEXZP	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC2YSTF	HOP-62	Investigative	[1]
Malignant melanoma	DCXPP7O	LOX IMVI	Investigative	[1]
Melanoma	DCS7NVV	SK-MEL-2	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCQHAWJ	NCI-H322M	Investigative	[1]
Non-small cell lung carcinoma	DCZ3N1U	HOP-92	Investigative	[1]
Papillary renal cell carcinoma	DCDFJ89	ACHN	Investigative	[1]
Prostate carcinoma	DCMX3US	PC-3	Investigative	[1]
Colon adenocarcinoma	DC2OJOQ	COLO 205	Investigative	[7]
Colon carcinoma	DCYEYNI	KM12	Investigative	[7]
Invasive ductal carcinoma	DC4QF8Q	HS 578T	Investigative	[7]
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⏷ Show the Full List of 21 DrugCom(s)

References

1	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.
2	ClinicalTrials.gov (NCT00715637) Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDEStudy. U.S. National Institutes of Health.
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	Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
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	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.