Details of the Drug Combination

General Information of Drug Combination (ID: DC1AOQH)

• Drug Combination Name: Tobramycin + Aciclovir
• Indication: Corneal Ulcer; Status: Phase 1 [1]
• Component Drugs:
  Tobramycin (DMUI0CH): Small molecular drug
  Aciclovir (DMYLOVR): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tobramycin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Blepharoconjunctivitis	N.A.	Approved	[2]
Corneal abrasion	NA06.4	Approved	[2]
Dacryocystitis	N.A.	Approved	[2]
Demodex blepharitis	1G07	Approved	[2]
Neonatal sepsis	N.A.	Approved	[2]
Peritonitis	N.A.	Approved	[2]
Rosacea	ED90.0	Approved	[2]
Staphylococcal pneumonia	N.A.	Approved	[2]
Staphylococcus aureus infection	N.A.	Approved	[2]

Tobramycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 30S ribosomal RNA (Bact 30S rRNA)	TTOVFH2	NOUNIPROTAC	Modulator	[12]

Tobramycin Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[13]
Aminoglycoside O-phosphotransferase (aphA6)	DEWPAJD	KKA6_ACIBA	Metabolism	[14]
Aminoglycoside phosphotransferase (aph-Ib)	DE5WGIM	A0A075C7U3_CAMJU	Metabolism	[15]
Kanamycin/gentamycin-resistance enzyme (aacA)	DECXWN8	J3S7E2_CAMCO	Metabolism	[15]
Aminoglycoside N-acetyltransferase (aacC2)	DEJADS9	AAC6_ACIBA	Metabolism	[14]

Tobramycin Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[11]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[11]
Beta-2-microglobulin (B2M)	OTDWN6NX	B2MG_HUMAN	Increases Expression	[16]
Survival motor neuron protein (SMN2)	OT54RLO1	SMN_HUMAN	Increases Expression	[17]
Phospholipase A2 (PLA2G1B)	OT1GG9FK	PA21B_HUMAN	Increases ADR	[18]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1)	OT9HYT7A	PLCB1_HUMAN	Increases ADR	[18]
Lysozyme C (LYZ)	OTD7H0G6	LYSC_HUMAN	Increases ADR	[18]
L-lactate dehydrogenase A chain (LDHA)	OTN7K4XB	LDHA_HUMAN	Increases ADR	[18]
Beta-hexosaminidase (nag1)	OTQCIZOD	P87258_TRIHA	Increases ADR	[18]

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	[19]
Varicella-zoster virus DNA polymerase (VZV ORF28)	TTHPJTK	DPOL_VZVD	Modulator	[20]

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	[21]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[22]
Organic anion transporter 2 (SLC22A7)	DT0OC1Q	S22A7_HUMAN	Substrate	[23]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[24]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[25]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[25]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[26]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[24]
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)	DTW7AE3	AAAT_HUMAN	Substrate	[27]

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	[28]
Indoleamine 2,3-dioxygenase 1 (IDO1)	OT91DBN7	I23O1_HUMAN	Decreases Activity	[29]
3-hydroxyanthranilate 3,4-dioxygenase (HAAO)	OTK9Y6SG	3HAO_HUMAN	Decreases Activity	[29]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[30]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[30]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[30]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[30]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[30]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[30]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[31]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[30]
Myelin basic protein (MBP)	OTFZCEDB	MBP_HUMAN	Increases ADR	[18]

References

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• [22] 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.
• [23] Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 2008 Apr;73(4):1151-8.
• [24] 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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