Details of the Drug Combination

General Information of Drug Combination (ID: DCHF1HD)

• Drug Combination Name: Aciclovir + PF-02545920
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Aciclovir (DMYLOVR): Small molecular drug
  PF-02545920 (DMJPE61): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.68
  Bliss Independence Score: 3.68
  Loewe Additivity Score: 20.64
  LHighest Single Agent (HSA) Score: 20.68

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Aciclovir

Disease Entry	ICD 11	Status	REF
Genital herpes	1A94	Approved	[2]
Herpes simplex encephalitis	N.A.	Approved	[3]
Herpes simplex infection	1F00	Approved	[4]
Herpes simplex labialis	1F00.01	Approved	[5]
Varicella	1E90	Approved	[6]
Virus infection	1A24-1D9Z	Approved	[7]
Herpes simplex virus infection	1F00	Phase 3	[8]

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	[12]

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	[13]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[14]
Organic anion transporter 2 (SLC22A7)	DT0OC1Q	S22A7_HUMAN	Substrate	[15]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[16]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[17]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[17]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[18]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[16]
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)	DTW7AE3	AAAT_HUMAN	Substrate	[19]

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	[20]
Indoleamine 2,3-dioxygenase 1 (IDO1)	OT91DBN7	I23O1_HUMAN	Decreases Activity	[21]
3-hydroxyanthranilate 3,4-dioxygenase (HAAO)	OTK9Y6SG	3HAO_HUMAN	Decreases Activity	[21]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[22]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[22]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[22]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[22]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[22]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[22]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[23]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[22]
Myelin basic protein (MBP)	OTFZCEDB	MBP_HUMAN	Increases ADR	[24]

Indication(s) of PF-02545920

Disease Entry	ICD 11	Status	REF
Huntington disease	8A01.10	Phase 2	[9]
Schizophrenia	6A20	Phase 2	[10]

PF-02545920 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 10A (PDE10)	TTJW4LU	PDE10_HUMAN	Inhibitor	[9]

PF-02545920 Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Lipid transferase CIDEA (CIDEA)	OTDUTSOV	CIDEA_HUMAN	Increases Expression	[25]
Type II iodothyronine deiodinase (DIO2)	OTGPNSLH	IOD2_HUMAN	Increases Expression	[25]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Increases Expression	[25]

References

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• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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• [15] Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 2008 Apr;73(4):1151-8.
• [16] 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] 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.
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• [25] A novel thermoregulatory role for PDE10A in mouse and human adipocytes. EMBO Mol Med. 2016 Jul 1;8(7):796-812. doi: 10.15252/emmm.201506085. Print 2016 Jul.