Details of the Drug Combination

General Information of Drug Combination (ID: DC29TSQ)

• Drug Combination Name: Pentamidine + Emetine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pentamidine (DMHZJCG): Small molecular drug
  Emetine (DMCT2YF): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 6.05
  Bliss Independence Score: 6.05
  Loewe Additivity Score: 9.7
  LHighest Single Agent (HSA) Score: 9.7

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pentamidine

Disease Entry	ICD 11	Status	REF
African trypanosomiasis	1F51	Approved	[2]
Fungal infection	1F29-1F2F	Approved	[3]
Pneumocystis pneumonia	CA40.20	Approved	[2]
Human immunodeficiency virus infection	1C62	Withdrawn from market	[4]

Pentamidine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tryptase alpha/beta-1 (Tryptase)	TTM1TDX	TRYB1_HUMAN	Inhibitor	[6]

Pentamidine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[7]

Pentamidine Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[9]

Pentamidine Interacts with 26 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[10]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[10]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[10]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[10]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[5]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[5]
Serine protease hepsin (HPN)	OT7QNA61	HEPS_HUMAN	Increases Expression	[5]
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Decreases Expression	[5]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[5]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Decreases Expression	[5]
Lanosterol synthase (LSS)	OT9W2SFH	LSS_HUMAN	Decreases Expression	[5]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[5]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[5]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[5]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[5]
Nibrin (NBN)	OT73B5MD	NBN_HUMAN	Affects Localization	[11]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[12]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Affects Expression	[13]
Interferon gamma receptor 1 (IFNGR1)	OTCTQBWW	INGR1_HUMAN	Increases Expression	[14]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Affects Localization	[11]
Double-strand break repair protein MRE11 (MRE11)	OTGU8TZM	MRE11_HUMAN	Decreases Activity	[11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[15]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Decreases Activity	[11]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[16]
Histone acetyltransferase KAT5 (KAT5)	OTL7257A	KAT5_HUMAN	Decreases Activity	[11]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Increases Activity	[17]

Indication(s) of Emetine

Disease Entry	ICD 11	Status	REF
Hepatitis virus infection	1E50-1E51	Approved	[4]

Emetine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[19]

Emetine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[20]

Emetine Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK)	OT9QIHEQ	RECK_HUMAN	Decreases Expression	[21]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[22]
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Increases Degradation	[23]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[21]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Decreases Expression	[18]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[24]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[18]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Decreases Expression	[18]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[25]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Decreases Expression	[18]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[18]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[18]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[21]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[21]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[21]

References

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• [2] Pentamidine FDA Label
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• [21] Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways. Chem Biol Interact. 2015 Dec 5;242:25-33. doi: 10.1016/j.cbi.2015.08.014. Epub 2015 Aug 30.
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