Details of the Drug Combination

General Information of Drug Combination (ID: DC34BDD)

• Drug Combination Name: Metformin + Aciclovir
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Metformin (DM89QE1): Small molecular drug
  Aciclovir (DMYLOVR): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 21.36
  Bliss Independence Score: 21.36
  Loewe Additivity Score: 31.35
  LHighest Single Agent (HSA) Score: 31.35

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Metformin

Disease Entry	ICD 11	Status	REF
Colorectal carcinoma	N.A.	Approved	[2]
Non-insulin dependent diabetes	5A11	Approved	[2]
Ovarian serous cystadenocarcinoma	N.A.	Approved	[2]
Prostate carcinoma	N.A.	Approved	[2]
Type-2 diabetes	5A11	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]

Metformin Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Acetyl-CoA carboxylase 2 (ACACB)	TTY84UG	ACACB_HUMAN	Activator	[11]
Solute carrier family 47 member 1 (SLC47A1)	TTMHCGA	S47A1_HUMAN	Modulator	[12]
HUMAN mannose receptor (MRC1)	TTKV8W5	MRC1_HUMAN	Inhibitor	[4]

Metformin Interacts with 9 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[13]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[14]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[15]
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[16]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[14]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[17]
Thiamine transporter 1 (SLC19A2)	DTLA4Q2	S19A2_HUMAN	Substrate	[18]
Thiamine transporter 2 (SLC19A3)	DT39CEA	S19A3_HUMAN	Substrate	[18]
Equilibrative nucleoside transporter 4 (SLC29A4)	DT3EAQP	S29A4_HUMAN	Substrate	[19]

Indication(s) of Aciclovir

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

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	[20]
Varicella-zoster virus DNA polymerase (VZV ORF28)	TTHPJTK	DPOL_VZVD	Modulator	[21]

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	[22]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[23]
Organic anion transporter 2 (SLC22A7)	DT0OC1Q	S22A7_HUMAN	Substrate	[24]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[17]
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	[17]
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	[32]

References

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• [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.
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• [26] Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs. Drug Metab Dispos. 2012 Mar;40(3):617-24.
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