Details of the Drug Combination

General Information of Drug Combination (ID: DCRIFBN)

• Drug Combination Name: Entacapone + Abacavir
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Entacapone (DMLBVKQ): Small molecular drug
  Abacavir (DMMN36E): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 1.98
  Bliss Independence Score: 1.98
  Loewe Additivity Score: 16.84
  LHighest Single Agent (HSA) Score: 16.84

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Entacapone

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Approved	[2]

Entacapone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Catechol-O-methyl-transferase (COMT)	TTKWFB8	COMT_HUMAN	Inhibitor	[6]

Entacapone Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[8]

Entacapone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[5]

Entacapone Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM)	OTR1XD9B	GPAT1_HUMAN	Decreases Expression	[9]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[10]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[10]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[10]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[10]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[10]
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Decreases Activity	[11]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[10]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[10]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Decreases Expression	[10]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[10]

Indication(s) of Abacavir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[3]

Abacavir 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	Inhibitor	[14]

Abacavir Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[16]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[17]

Abacavir Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[18]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[19]
Alcohol dehydrogenase class-V (ADH6)	DE017IC	ADH6_HUMAN	Metabolism	[18]

Abacavir Interacts with 26 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Increases Response To Substance	[20]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Increases Expression	[21]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases Expression	[21]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[21]
Telomerase reverse transcriptase (TERT)	OT085VVA	TERT_HUMAN	Decreases Activity	[22]
Retinal dehydrogenase 2 (ALDH1A2)	OTJB560Z	AL1A2_HUMAN	Decreases Expression	[12]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[23]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[24]
Synaptophysin (SYP)	OTFJKMO4	SYPH_HUMAN	Increases Expression	[22]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[12]
HLA class I histocompatibility antigen, C alpha chain (HLA-C)	OTV38BUJ	HLAC_HUMAN	Affects Binding	[25]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Increases Expression	[22]
Homeobox protein Hox-B9 (HOXB9)	OTMVHQOU	HXB9_HUMAN	Increases Expression	[12]
Paired box protein Pax-3 (PAX3)	OTN5PJZV	PAX3_HUMAN	Decreases Expression	[12]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[12]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[12]
Fibroblast growth factor 8 (FGF8)	OTFU0IUW	FGF8_HUMAN	Increases Expression	[12]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Decreases Expression	[12]
Transcription factor 15 (TCF15)	OTA6UCWC	TCF15_HUMAN	Decreases Expression	[12]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[24]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Increases Expression	[12]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[12]
Forkhead box protein C2 (FOXC2)	OT83P1E0	FOXC2_HUMAN	Decreases Expression	[12]
Neurogenin-2 (NEUROG2)	OTAEMIGT	NGN2_HUMAN	Increases Expression	[12]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Affects Response To Substance	[26]
HLA class I histocompatibility antigen protein P5 (HCP5)	OTV0YRI8	HCP5_HUMAN	Increases ADR	[27]

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] 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: 6647).
• [3] Abacavir (marketed as Ziagen) and Abacavir-containing Medications. FDA. 2008.
• [4] Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism. Neurology. 2005 Dec 13;65(11):1820-2. doi: 10.1212/01.wnl.0000187066.81162.70.
• [5] Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos. 2005 Jul;33(7):1017-26.
• [6] Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771.
• [7] Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol-O-Methyltransferase Inhibitors. Drug Metab Dispos. 2017 Dec;45(12):1282-1291.
• [8] Organic Anion Transporter 2-Mediated Hepatic Uptake Contributes to the Clearance of High-Permeability-Low-Molecular-Weight Acid and Zwitterion Drugs: Evaluation Using 25 Drugs. J Pharmacol Exp Ther. 2018 Nov;367(2):322-334.
• [9] Effect of the Catechol-O-Methyltransferase Inhibitors Tolcapone and Entacapone on Fatty Acid Metabolism in HepaRG Cells. Toxicol Sci. 2018 Aug 1;164(2):477-488.
• [10] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [11] Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration. Brain Res. 2013 Feb 25;1497:1-14. doi: 10.1016/j.brainres.2012.11.043. Epub 2012 Dec 1.
• [12] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [13] Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Antivir Ther. 2003 Aug;8(4):323-31.
• [14] Quadruple nucleos(t)ide reverse transcriptase inhibitors-only regimen of tenofovir plus zidovudine/lamivudine/abacavir in heavily pre-treated HIV-1 infected patients: salvage therapy or backbone only Curr HIV Res. 2009 May;7(3):320-6.
• [15] The transport of anti-HIV drugs across blood-CNS interfaces: summary of current knowledge and recommendations for further research. Antiviral Res. 2009 May;82(2):A99-109.
• [16] QSAR analysis and molecular modeling of ABCG2-specific inhibitors. Adv Drug Deliv Rev. 2009 Jan 31;61(1):34-46.
• [17] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [18] A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351-71.
• [19] Product characteristics of Triumeq.
• [20] Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002 Mar 30;359(9312):1121-2. doi: 10.1016/S0140-6736(02)08158-8.
• [21] Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy. HIV Med. 2009 Nov;10(10):627-33.
• [22] The antiretroviral nucleoside analogue Abacavir reduces cell growth and promotes differentiation of human medulloblastoma cells. Int J Cancer. 2009 Jul 1;125(1):235-43. doi: 10.1002/ijc.24331.
• [23] Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
• [24] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [25] Harvesting candidate genes responsible for serious adverse drug reactions from a chemical-protein interactome. PLoS Comput Biol. 2009 Jul;5(7):e1000441. doi: 10.1371/journal.pcbi.1000441. Epub 2009 Jul 24.
• [26] Intracellular cytokines may model immunoregulation of abacavir hypersensitivity in HIV-infected subjects. J Allergy Clin Immunol. 2005 May;115(5):1081-7. doi: 10.1016/j.jaci.2004.12.1140.
• [27] The HCP5 single-nucleotide polymorphism: a simple screening tool for prediction of hypersensitivity reaction to abacavir. J Infect Dis. 2008 Sep 15;198(6):864-7. doi: 10.1086/591184.