Details of the Drug Combination

General Information of Drug Combination (ID: DCN1DBM)

• Drug Combination Name: Picoplatin + Abacavir
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Picoplatin (DM0PIY6): Small molecular drug
  Abacavir (DMMN36E): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 7.28
  Bliss Independence Score: 7.28
  Loewe Additivity Score: 20.93
  LHighest Single Agent (HSA) Score: 20.95

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Picoplatin

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Phase 3	[2]
Ovarian cancer	2C73	Phase 3	[2]
Prostate cancer	2C82.0	Phase 3	[2]
Small-cell lung cancer	2C25.Y	Phase 3	[2]

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	[6]

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	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[9]

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	[10]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[11]
Alcohol dehydrogenase class-V (ADH6)	DE017IC	ADH6_HUMAN	Metabolism	[10]

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	[12]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Increases Expression	[13]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases Expression	[13]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[13]
Telomerase reverse transcriptase (TERT)	OT085VVA	TERT_HUMAN	Decreases Activity	[14]
Retinal dehydrogenase 2 (ALDH1A2)	OTJB560Z	AL1A2_HUMAN	Decreases Expression	[4]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[15]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[16]
Synaptophysin (SYP)	OTFJKMO4	SYPH_HUMAN	Increases Expression	[14]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[4]
HLA class I histocompatibility antigen, C alpha chain (HLA-C)	OTV38BUJ	HLAC_HUMAN	Affects Binding	[17]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Increases Expression	[14]
Homeobox protein Hox-B9 (HOXB9)	OTMVHQOU	HXB9_HUMAN	Increases Expression	[4]
Paired box protein Pax-3 (PAX3)	OTN5PJZV	PAX3_HUMAN	Decreases Expression	[4]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[4]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[4]
Fibroblast growth factor 8 (FGF8)	OTFU0IUW	FGF8_HUMAN	Increases Expression	[4]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Decreases Expression	[4]
Transcription factor 15 (TCF15)	OTA6UCWC	TCF15_HUMAN	Decreases Expression	[4]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[16]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Increases Expression	[4]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[4]
Forkhead box protein C2 (FOXC2)	OT83P1E0	FOXC2_HUMAN	Decreases Expression	[4]
Neurogenin-2 (NEUROG2)	OTAEMIGT	NGN2_HUMAN	Increases Expression	[4]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Affects Response To Substance	[18]
HLA class I histocompatibility antigen protein P5 (HCP5)	OTV0YRI8	HCP5_HUMAN	Increases ADR	[19]

References

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• [2] ClinicalTrials.gov (NCT00465491) Study of Picoplatin Efficacy After Relapse. U.S. National Institutes of Health.
• [3] Abacavir (marketed as Ziagen) and Abacavir-containing Medications. FDA. 2008.
• [4] 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.
• [5] Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Antivir Ther. 2003 Aug;8(4):323-31.
• [6] 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.
• [7] 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.
• [8] QSAR analysis and molecular modeling of ABCG2-specific inhibitors. Adv Drug Deliv Rev. 2009 Jan 31;61(1):34-46.
• [9] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [10] A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351-71.
• [11] Product characteristics of Triumeq.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.