Details of the Drug Combination

General Information of Drug Combination (ID: DCXM1F4)

Drug Combination Name

Indazole derivative 5 Uracil mustard

Indication

Disease Entry	Status	REF
Lung adenocarcinoma	Investigative	[1]

Component Drugs

Indazole derivative 5 DMM1I8R

Uracil mustard DMHL7OB

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: EKVX

Zero Interaction Potency (ZIP) Score: 7.7

Bliss Independence Score: 13.46

Loewe Additivity Score: 8.92

LHighest Single Agent (HSA) Score: 14.2

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indazole derivative 5 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ABL T315I mutant (ABL T315I)	TTZJTWA	ABL1_HUMAN	Inhibitor	[4]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)	TTIV39N	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[4]
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Indication(s) of Uracil mustard

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

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
Adult T acute lymphoblastic leukemia	DCQ3Y10	MOLT-4	Investigative	[7]
Astrocytoma	DC5U3NI	SNB-19	Investigative	[7]
Chronic myelogenous leukemia	DCSH966	K-562	Investigative	[7]
Glioblastoma	DC5IAIX	SNB-75	Investigative	[7]
Glioma	DCW50SF	SF-295	Investigative	[7]
Colon carcinoma	DCTVD7G	KM12	Investigative	[8]
Amelanotic melanoma	DCQJXKW	MDA-MB-435	Investigative	[1]
Large cell lung carcinoma	DCE9XTK	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCIYHHR	NCI-H522	Investigative	[1]
Malignant melanoma	DCSWWEM	UACC62	Investigative	[1]
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⏷ Show the Full List of 10 DrugCom(s)

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: 7621).
3	Uracil mustard FDA Label
4	Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
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	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.
8	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.