Details of the Drug Combination

General Information of Drug Combination (ID: DCBQAEL)

• Drug Combination Name: Efavirenz + Bosentan
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Efavirenz (DMC0GSJ): Small molecular drug
  Bosentan (DMIOGBU): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 35.56
  Bliss Independence Score: 35.56
  Loewe Additivity Score: 50.11
  LHighest Single Agent (HSA) Score: 50.11

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Efavirenz

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[2]

Efavirenz Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Modulator	[5]

Efavirenz Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
Multidrug resistance-associated protein 3 (ABCC3)	DTQ3ZHF	MRP3_HUMAN	Substrate	[7]

Efavirenz Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[9]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[10]

Efavirenz Interacts with 32 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[11]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[12]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[12]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[13]
Dynamin-1-like protein (DNM1L)	OTXK1Q1G	DNM1L_HUMAN	Affects Localization	[14]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[15]
Dynamin-like 120 kDa protein, mitochondrial (OPA1)	OTJGNWPW	OPA1_HUMAN	Increases Expression	[14]
Mitofusin-2 (MFN2)	OTPYN8A3	MFN2_HUMAN	Increases Expression	[14]
Thyroglobulin (TG)	OT3ELHIJ	THYG_HUMAN	Increases Expression	[16]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[17]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Secretion	[18]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Secretion	[18]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[15]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Decreases Expression	[18]
Thyroid peroxidase (TPO)	OTJJLL20	PERT_HUMAN	Increases Expression	[16]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Secretion	[18]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[18]
Hepatocyte growth factor (HGF)	OTGHUA23	HGF_HUMAN	Increases Secretion	[18]
Thyrotropin receptor (TSHR)	OT0BC8LB	TSHR_HUMAN	Increases Expression	[16]
Calnexin (CANX)	OTYP1F6J	CALX_HUMAN	Affects Localization	[14]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[14]
Lon protease homolog, mitochondrial (LONP1)	OT665WYT	LONM_HUMAN	Increases Expression	[14]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[18]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Expression	[18]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Decreases Expression	[18]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[15]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Decreases Expression	[18]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Decreases Expression	[18]
Regulator of microtubule dynamics protein 3 (RMDN3)	OTKO7AUM	RMD3_HUMAN	Increases Expression	[14]
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5)	OTQR6ENW	M3K5_HUMAN	Increases Phosphorylation	[15]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Expression	[14]
Mitochondrial fission 1 protein (FIS1)	OT2HL10J	FIS1_HUMAN	Increases Expression	[14]

Indication(s) of Bosentan

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Approved	[3]
Pulmonary hypertension	BB01	Approved	[4]
Scleroderma	4A42	Investigative	[4]

Bosentan Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Endothelin A receptor (EDNRA)	TTKRD0G	EDNRA_HUMAN	Modulator	[5]
Endothelin B receptor (EDNRB)	TT3ZTGU	EDNRB_HUMAN	Modulator	[5]

Bosentan Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[20]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[20]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[20]

Bosentan Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[21]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[22]

Bosentan Interacts with 71 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[23]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Decreases Expression	[19]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Expression	[19]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Activity	[24]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases ADR	[25]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[23]
Serine/threonine-protein kinase DCLK1 (DCLK1)	OTVSPS98	DCLK1_HUMAN	Affects Expression	[19]
Kynurenine 3-monooxygenase (KMO)	OT3MRMM9	KMO_HUMAN	Affects Expression	[19]
Carbonic anhydrase 12 (CA12)	OT6WNFU8	CAH12_HUMAN	Affects Expression	[19]
All-trans-retinol dehydrogenase ADH1B (ADH1B)	OTV3TB81	ADH1B_HUMAN	Decreases Expression	[19]
Alcohol dehydrogenase 1C (ADH1C)	OTO1DV7F	ADH1G_HUMAN	Decreases Expression	[19]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Decreases Expression	[19]
Complement component C9 (C9)	OT7I5FDX	CO9_HUMAN	Affects Expression	[19]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[19]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[19]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Affects Expression	[19]
Fructose-bisphosphate aldolase B (ALDOB)	OT7FR69A	ALDOB_HUMAN	Decreases Expression	[19]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[19]
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Decreases Expression	[19]
Glutathione peroxidase 1 (GPX1)	OTE2O72Q	GPX1_HUMAN	Decreases Expression	[19]
Alcohol dehydrogenase 1A (ADH1A)	OTTS983E	ADH1A_HUMAN	Decreases Expression	[19]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Increases Expression	[19]
All-trans-retinol dehydrogenase ADH4 (ADH4)	OTKDKKNG	ADH4_HUMAN	Decreases Expression	[19]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[19]
Glutathione S-transferase theta-2 (GSTT2)	OTANW3TJ	GST2_HUMAN	Decreases Expression	[19]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[19]
Microsomal glutathione S-transferase 1 (MGST1)	OTGN1KVZ	MGST1_HUMAN	Decreases Expression	[19]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1)	OTNAZVKB	3BHS1_HUMAN	Affects Expression	[19]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[19]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Affects Expression	[19]
Tyrosine aminotransferase (TAT)	OT2CJ91O	ATTY_HUMAN	Affects Expression	[19]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Expression	[19]
Cytochrome P450 7A1 (CYP7A1)	OT8Z5KLD	CP7A1_HUMAN	Decreases Expression	[19]
Macrophage mannose receptor 1 (MRC1)	OTTVCOPT	MRC1_HUMAN	Affects Expression	[19]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Affects Expression	[19]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Decreases Expression	[19]
G0/G1 switch protein 2 (G0S2)	OT8FL49L	G0S2_HUMAN	Affects Expression	[19]
Sodium- and chloride-dependent GABA transporter 1 (SLC6A1)	OTLCJJF3	SC6A1_HUMAN	Affects Expression	[19]
Pyruvate kinase PKLR (PKLR)	OTTTM1QI	KPYR_HUMAN	Affects Expression	[19]
Carbamoyl-phosphate synthase , mitochondrial (CPS1)	OTXV8NSR	CPSM_HUMAN	Decreases Expression	[19]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Affects Expression	[19]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Expression	[19]
Hepatocyte nuclear factor 4-alpha (HNF4A)	OTY1TOAB	HNF4A_HUMAN	Decreases Expression	[19]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Increases Expression	[19]
Sulfotransferase 1E1 (SULT1E1)	OTGPJ517	ST1E1_HUMAN	Affects Expression	[19]
Achaete-scute homolog 1 (ASCL1)	OTI4X44G	ASCL1_HUMAN	Affects Expression	[19]
Oxysterols receptor LXR-beta (NR1H2)	OT4APA60	NR1H2_HUMAN	Decreases Expression	[19]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[19]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Affects Expression	[19]
Metallothionein-1X (MT1X)	OT9AKFVS	MT1X_HUMAN	Increases Expression	[19]
Complement factor H-related protein 3 (CFHR3)	OTYL8SDO	FHR3_HUMAN	Affects Expression	[19]
Oxysterols receptor LXR-alpha (NR1H3)	OT54YZ9I	NR1H3_HUMAN	Decreases Expression	[19]
Nuclear factor 1 X-type (NFIX)	OT1DPZAE	NFIX_HUMAN	Decreases Expression	[19]
Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2)	OTJ8LX4N	PCKGM_HUMAN	Decreases Expression	[19]
Organic solute transporter subunit alpha (SLC51A)	OTDJRZ0P	OSTA_HUMAN	Increases Expression	[19]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[19]
Liver-expressed antimicrobial peptide 2 (LEAP2)	OTUOPIS5	LEAP2_HUMAN	Affects Expression	[19]
N-acetylmuramoyl-L-alanine amidase (PGLYRP2)	OTF8319A	PGRP2_HUMAN	Affects Expression	[19]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Expression	[19]
Normal mucosa of esophagus-specific gene 1 protein (C15ORF48)	OT85J32K	NMES1_HUMAN	Affects Expression	[19]
ATP-binding cassette sub-family G member 5 (ABCG5)	OT1OMY93	ABCG5_HUMAN	Affects Expression	[19]
2-aminomuconic semialdehyde dehydrogenase (ALDH8A1)	OTINY3MW	AL8A1_HUMAN	Affects Expression	[19]
Cytochrome P450 3A43 (CYP3A43)	OTMXADGA	CP343_HUMAN	Affects Expression	[19]
NADPH oxidase 4 (NOX4)	OTTYQ097	NOX4_HUMAN	Decreases Expression	[19]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Decreases Expression	[19]
Solute carrier family 22 member 7 (SLC22A7)	OTKTNH1W	S22A7_HUMAN	Affects Expression	[19]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Decreases Expression	[26]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[26]
Coxsackievirus and adenovirus receptor (CXADR)	OT9ZP02A	CXAR_HUMAN	Decreases Expression	[27]
Hepatic sodium/bile acid cotransporter (SLC10A1)	OTUJVMCL	NTCP_HUMAN	Decreases Expression	[26]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Decreases Expression	[26]

References

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• [4] Bosentan FDA Label
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• [15] Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes. Toxicol Appl Pharmacol. 2011 Dec 1;257(2):227-34. doi: 10.1016/j.taap.2011.09.008. Epub 2011 Sep 19.
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• [21] Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
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