Details of the Drug Combination

General Information of Drug Combination (ID: DCY86ZW)

• Drug Combination Name: Pyrimethamine + Miconazole
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  Pyrimethamine (DM5X7VY): Small molecular drug
  Miconazole (DMPMYE8): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 1.491
  Bliss Independence Score: 6.802
  Loewe Additivity Score: 0.11
  LHighest Single Agent (HSA) Score: 5.022

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pyrimethamine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]

Pyrimethamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Folate receptor alpha (FOLR1)	TTVC37M	FOLR1_HUMAN	Modulator	[5]

Pyrimethamine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[6]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[7]

Pyrimethamine Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Activity	[8]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[9]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[10]
Suppressor of cytokine signaling 3 (SOCS3)	OTY183WJ	SOCS3_HUMAN	Decreases Expression	[11]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[12]
Beta-hexosaminidase subunit beta (HEXB)	OTROYLCR	HEXB_HUMAN	Affects Binding	[13]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Increases Activity	[14]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[15]
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Affects Expression	[16]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[17]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[17]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[14]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[14]
Multidrug and toxin extrusion protein 2 (SLC47A2)	OTF2CNRD	S47A2_HUMAN	Decreases Activity	[8]
Proton-coupled folate transporter (SLC46A1)	OT049V7Y	PCFT_HUMAN	Decreases Activity	[18]

Indication(s) of Miconazole

Disease Entry	ICD 11	Status	REF
Cutaneous candidiasis	1F23.14	Approved	[3]
Fungal infection	1F29-1F2F	Approved	[4]
Mycoses	1F2Z	Approved	[3]
Onychomycosis	EE12.1	Approved	[3]
Tinea corporis	1F28.Y	Approved	[3]
Tinea cruris	1F28.3	Approved	[3]
Tinea versicolor	1F2D.0	Approved	[3]
Tinea pedis	1F28.2	Investigative	[3]

Miconazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Candida Cytochrome P450 51 (Candi ERG11)	TTTSOUD	CP51_CANAL	Modulator	[5]

Miconazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[19]

Miconazole Interacts with 17 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[20]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[21]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[22]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Decreases Expression	[23]
Tyrosine aminotransferase (TAT)	OT2CJ91O	ATTY_HUMAN	Decreases Expression	[23]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Decreases Expression	[23]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[24]
Adenylate cyclase type 9 (ADCY9)	OT1IZT5K	ADCY9_HUMAN	Increases Activity	[25]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Activity	[26]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[27]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[27]
Cathepsin D (CTSD)	OTQZ36F3	CATD_HUMAN	Increases Expression	[28]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[28]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[29]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[28]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Lipidation	[28]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Decreases Response To Substance	[30]

References

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• [3] Miconazole FDA Label
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2449).
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