Details of the Drug Combination

General Information of Drug Combination (ID: DC2H6PR)

• Drug Combination Name: Sumatriptan + Efavirenz
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Sumatriptan (DMVYXR8): Small molecular drug
  Efavirenz (DMC0GSJ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 11.01
  Bliss Independence Score: 11.01
  Loewe Additivity Score: 25.59
  LHighest Single Agent (HSA) Score: 25.59

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sumatriptan

Disease Entry	ICD 11	Status	REF
Cluster headache	8A81.0	Approved	[2]
Migraine	8A80	Approved	[3]
Migraine disorder	N.A.	Approved	[2]

Sumatriptan Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Agonist	[5]

Sumatriptan 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]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[7]

Sumatriptan Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Decreases Expression	[8]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Decreases Expression	[9]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3)	OTA6HYBA	GBB3_HUMAN	Increases Response	[10]
5-hydroxytryptamine receptor 1F (HTR1F)	OTALAXPA	5HT1F_HUMAN	Increases ADR	[11]
Calcitonin gene-related peptide 1 (CALCA)	OTQSXM9Z	CALCA_HUMAN	Increases ADR	[11]

Indication(s) of Efavirenz

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[4]

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	[12]

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	[13]
Multidrug resistance-associated protein 3 (ABCC3)	DTQ3ZHF	MRP3_HUMAN	Substrate	[14]

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	[15]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[16]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[17]

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	[18]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[19]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[19]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[20]
Dynamin-1-like protein (DNM1L)	OTXK1Q1G	DNM1L_HUMAN	Affects Localization	[21]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[22]
Dynamin-like 120 kDa protein, mitochondrial (OPA1)	OTJGNWPW	OPA1_HUMAN	Increases Expression	[21]
Mitofusin-2 (MFN2)	OTPYN8A3	MFN2_HUMAN	Increases Expression	[21]
Thyroglobulin (TG)	OT3ELHIJ	THYG_HUMAN	Increases Expression	[23]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[24]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Secretion	[25]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Secretion	[25]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[22]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Decreases Expression	[25]
Thyroid peroxidase (TPO)	OTJJLL20	PERT_HUMAN	Increases Expression	[23]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Secretion	[25]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[25]
Hepatocyte growth factor (HGF)	OTGHUA23	HGF_HUMAN	Increases Secretion	[25]
Thyrotropin receptor (TSHR)	OT0BC8LB	TSHR_HUMAN	Increases Expression	[23]
Calnexin (CANX)	OTYP1F6J	CALX_HUMAN	Affects Localization	[21]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[21]
Lon protease homolog, mitochondrial (LONP1)	OT665WYT	LONM_HUMAN	Increases Expression	[21]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[25]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Expression	[25]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Decreases Expression	[25]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[22]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Decreases Expression	[25]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Decreases Expression	[25]
Regulator of microtubule dynamics protein 3 (RMDN3)	OTKO7AUM	RMD3_HUMAN	Increases Expression	[21]
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5)	OTQR6ENW	M3K5_HUMAN	Increases Phosphorylation	[22]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Expression	[21]
Mitochondrial fission 1 protein (FIS1)	OT2HL10J	FIS1_HUMAN	Increases Expression	[21]

References

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• [21] Lon protease: a novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum stress. Br J Pharmacol. 2017 Dec;174(23):4409-4429. doi: 10.1111/bph.14045. Epub 2017 Nov 7.
• [22] 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.
• [23] Reverse transcriptase inhibitors down-regulate cell proliferation in vitro and in vivo and restore thyrotropin signaling and iodine uptake in human thyroid anaplastic carcinoma. J Clin Endocrinol Metab. 2005 Oct;90(10):5663-71. doi: 10.1210/jc.2005-0367. Epub 2005 Jul 19.
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• [25] Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antiviral Res. 2011 Aug;91(2):112-9. doi: 10.1016/j.antiviral.2011.04.018. Epub 2011 May 17.