Details of the Drug Combination

General Information of Drug Combination (ID: DCCLUNB)

• Drug Combination Name: Diazoxide + Abacavir
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Diazoxide (DML1538): Small molecular drug
  Abacavir (DMMN36E): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.04
  Bliss Independence Score: 0.04
  Loewe Additivity Score: 0.46
  LHighest Single Agent (HSA) Score: 0.46

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Diazoxide

Disease Entry	ICD 11	Status	REF
Congenital hyperinsulinism	5A4Y	Approved	[2]
Hyperinsulinemia	5A4Y	Approved	[2]
Hypertension	BA00-BA04	Approved	[3]
Hypertensive emergency	BA03	Approved	[2]
Insulinoma	2C10.1	Approved	[2]
Malignant essential hypertension	BA00	Approved	[2]

Diazoxide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Potassium channel unspecific (KC)	TT1VOHK	NOUNIPROTAC	Modulator	[5]

Diazoxide Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[6]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[6]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Activity	[7]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Secretion	[6]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[8]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[8]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Increases Expression	[7]
ATP-sensitive inward rectifier potassium channel 11 (KCNJ11)	OTPUUELV	KCJ11_HUMAN	Decreases Expression	[9]

Indication(s) of Abacavir

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

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	[12]

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	[13]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[14]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[15]

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	[16]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[17]
Alcohol dehydrogenase class-V (ADH6)	DE017IC	ADH6_HUMAN	Metabolism	[16]

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	[18]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Increases Expression	[19]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases Expression	[19]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[19]
Telomerase reverse transcriptase (TERT)	OT085VVA	TERT_HUMAN	Decreases Activity	[20]
Retinal dehydrogenase 2 (ALDH1A2)	OTJB560Z	AL1A2_HUMAN	Decreases Expression	[10]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[21]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[22]
Synaptophysin (SYP)	OTFJKMO4	SYPH_HUMAN	Increases Expression	[20]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[10]
HLA class I histocompatibility antigen, C alpha chain (HLA-C)	OTV38BUJ	HLAC_HUMAN	Affects Binding	[23]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Increases Expression	[20]
Homeobox protein Hox-B9 (HOXB9)	OTMVHQOU	HXB9_HUMAN	Increases Expression	[10]
Paired box protein Pax-3 (PAX3)	OTN5PJZV	PAX3_HUMAN	Decreases Expression	[10]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[10]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[10]
Fibroblast growth factor 8 (FGF8)	OTFU0IUW	FGF8_HUMAN	Increases Expression	[10]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Decreases Expression	[10]
Transcription factor 15 (TCF15)	OTA6UCWC	TCF15_HUMAN	Decreases Expression	[10]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[22]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Increases Expression	[10]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[10]
Forkhead box protein C2 (FOXC2)	OT83P1E0	FOXC2_HUMAN	Decreases Expression	[10]
Neurogenin-2 (NEUROG2)	OTAEMIGT	NGN2_HUMAN	Increases Expression	[10]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Affects Response To Substance	[24]
HLA class I histocompatibility antigen protein P5 (HCP5)	OTV0YRI8	HCP5_HUMAN	Increases ADR	[25]

References

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• [2] Diazoxide FDA Label
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• [20] 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.
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• [22] 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.
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• [24] 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.
• [25] 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.