Details of the Drug Combination

General Information of Drug Combination (ID: DCNN559)

• Drug Combination Name: Busulfan + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Busulfan (DMXYJ9C): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 30.97
  Bliss Independence Score: 30.97
  Loewe Additivity Score: 14.97
  LHighest Single Agent (HSA) Score: 14.97

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Busulfan

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[2]
Hematologic disease	3C0Z	Approved	[2]
Immunodeficiency	4A00-4A85	Approved	[2]
Leukemia	N.A.	Approved	[2]
Myeloproliferative syndrome	2A22	Approved	[3]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Systemic sclerosis	4A42	Approved	[2]
Neuroblastoma	2D11.2	Investigative	[2]
Retinoblastoma	2D02.2	Investigative	[2]

Busulfan Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[7]

Busulfan Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[9]
Glutathione S-transferase alpha-2 (GSTA2)	DEH49YS	GSTA2_HUMAN	Metabolism	[10]
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[11]
Microsomal glutathione S-transferase 2 (MGST2)	DE31KMQ	MGST2_HUMAN	Metabolism	[12]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[11]

Busulfan Interacts with 34 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Affects Abundance	[13]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Abundance	[13]
Microsomal glutathione S-transferase 2 (MGST2)	OT4UGTDO	MGST2_HUMAN	Decreases Response To Substance	[12]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Response To Substance	[14]
Serotransferrin (TF)	OT41PEMS	TRFE_HUMAN	Increases Expression	[15]
Inhibin beta A chain (INHBA)	OTSP64PQ	INHBA_HUMAN	Increases Expression	[15]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[15]
Antithrombin-III (SERPINC1)	OTDFATG0	ANT3_HUMAN	Affects Expression	[16]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[17]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[17]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[6]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[18]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Expression	[17]
Thrombospondin-1 (THBS1)	OT0ECWK3	TSP1_HUMAN	Increases Expression	[17]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[19]
Tissue factor pathway inhibitor (TFPI)	OTA0FX16	TFPI1_HUMAN	Decreases Expression	[17]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[19]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[6]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[6]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Activity	[20]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Activity	[20]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Increases Expression	[6]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Affects Expression	[6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[20]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Affects Expression	[6]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[21]
Signal transducer and activator of transcription 2 (STAT2)	OTO9G2RZ	STAT2_HUMAN	Decreases Expression	[6]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[19]
Metal regulatory transcription factor 1 (MTF1)	OTJWVLLF	MTF1_HUMAN	Decreases Expression	[6]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[6]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[6]
Pseudouridylate synthase 7 homolog (PUS7)	OTE5AQHJ	PUS7_HUMAN	Increases Expression	[22]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[23]
Rho GDP-dissociation inhibitor 1 (ARHGDIA)	OTEXWJDO	GDIR1_HUMAN	Affects Response To Substance	[21]

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[4]
Acute myeloid leukaemia	2A60	Approved	[5]
Adult acute monocytic leukemia	N.A.	Approved	[4]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[4]
Leukemia	N.A.	Approved	[4]

Idarubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[25]

Idarubicin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[26]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[27]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[27]

Idarubicin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[28]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[28]

Idarubicin Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[24]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[29]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Activity	[24]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[30]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Activity	[24]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[31]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Decreases Activity	[24]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[32]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[24]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Chronic myelogenous leukemia	DCJBRB5	KBM-7	Investigative	[1]

References

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• [4] Idarubicin FDA Label
• [5] 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: 7083).
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