Details of the Drug Combination

General Information of Drug Combination (ID: DCNLE0X)

• Drug Combination Name: Zaleplon + Aciclovir
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Zaleplon (DMGFWSM): Small molecular drug
  Aciclovir (DMYLOVR): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 15.92
  Bliss Independence Score: 15.92
  Loewe Additivity Score: 27.51
  LHighest Single Agent (HSA) Score: 27.51

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Zaleplon

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Approved	[2]
Sleep disorder, initiating and maintaining sleep	N.A.	Investigative	[3]

Zaleplon Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
GABA(A) receptor alpha-1 (GABRA1)	TT1MPAY	GBRA1_HUMAN	Modulator	[11]

Zaleplon Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[13]
Aldehyde oxidase (AOX1)	DEAWHS8	AOXA_HUMAN	Metabolism	[14]

Indication(s) of Aciclovir

Disease Entry	ICD 11	Status	REF
Genital herpes	1A94	Approved	[4]
Herpes simplex encephalitis	N.A.	Approved	[5]
Herpes simplex infection	1F00	Approved	[6]
Herpes simplex labialis	1F00.01	Approved	[7]
Varicella	1E90	Approved	[8]
Virus infection	1A24-1D9Z	Approved	[9]
Herpes simplex virus infection	1F00	Phase 3	[10]

Aciclovir Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Herpes simplex virus DNA polymerase UL30 (HSV UL30)	TTIU7X1	DPOL_HHV11	Modulator	[11]
Varicella-zoster virus DNA polymerase (VZV ORF28)	TTHPJTK	DPOL_VZVD	Modulator	[15]

Aciclovir Interacts with 9 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[16]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[17]
Organic anion transporter 2 (SLC22A7)	DT0OC1Q	S22A7_HUMAN	Substrate	[18]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[19]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[20]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[20]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[21]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[19]
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)	DTW7AE3	AAAT_HUMAN	Substrate	[22]

Aciclovir Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Transport	[23]
Indoleamine 2,3-dioxygenase 1 (IDO1)	OT91DBN7	I23O1_HUMAN	Decreases Activity	[24]
3-hydroxyanthranilate 3,4-dioxygenase (HAAO)	OTK9Y6SG	3HAO_HUMAN	Decreases Activity	[24]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[25]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[25]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[25]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[25]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[25]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[25]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[26]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[25]
Myelin basic protein (MBP)	OTFZCEDB	MBP_HUMAN	Increases ADR	[27]

References

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• [3] Zaleplon FDA Label
• [4] Genital herpes. BMJ Clin Evid. 2011 Apr 15;2011:1603.
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• [8] Neonatal varicella. Arch Dis Child. 2023 Oct 31:archdischild-2022-324820.
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• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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• [13] Drug Interactions Flockhart Table
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• [19] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
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• [22] Amino Acid Transporter ATB0,+ as a delivery system for drugs and prodrugs. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Dec;5(4):357-64.
• [23] Acyclovir is a substrate for the human breast cancer resistance protein (BCRP/ABCG2): implications for renal tubular transport and acyclovir-induced nephrotoxicity. Can J Physiol Pharmacol. 2011 Sep;89(9):675-80. doi: 10.1139/y11-045. Epub 2011 Aug 22.
• [24] Mechanisms by which acyclovir reduces the oxidative neurotoxicity and biosynthesis of quinolinic acid. Life Sci. 2007 Feb 13;80(10):918-25.
• [25] 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.
• [26] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
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