Details of the Drug Combination

General Information of Drug Combination (ID: DCCG7IG)

• Drug Combination Name: Methoxsalen + Mebendazole
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Methoxsalen (DME8FZ9): Small molecular drug
  Mebendazole (DMO14SG): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 15.75
  Bliss Independence Score: 15.75
  Loewe Additivity Score: 30.13
  LHighest Single Agent (HSA) Score: 30.13

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Methoxsalen

Disease Entry	ICD 11	Status	REF
Cutaneous T-cell lymphoma	2B01	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[3]
Psoriasis vulgaris	EA90	Approved	[2]

Methoxsalen Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2A6 (CYP2A6)	TTAQ6ZW	CP2A6_HUMAN	Binder	[7]

Methoxsalen Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[9]

Methoxsalen Interacts with 26 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Decreases Activity	[10]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[8]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[11]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Increases Expression	[8]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[8]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[12]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[12]
Class E basic helix-loop-helix protein 40 (BHLHE40)	OTITX14U	BHE40_HUMAN	Decreases Expression	[13]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[13]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[6]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[14]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[13]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[15]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[16]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[13]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Expression	[17]
Cytochrome P450 7A1 (CYP7A1)	OT8Z5KLD	CP7A1_HUMAN	Decreases Expression	[6]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[16]
Histidine ammonia-lyase (HAL)	OT1HXFCV	HUTH_HUMAN	Decreases Activity	[18]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Decreases Expression	[13]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[13]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[13]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[6]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[15]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Decreases Expression	[16]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Expression	[16]

Indication(s) of Mebendazole

Disease Entry	ICD 11	Status	REF
Ascariasis	1F62	Approved	[4]
Enterobiasis	1F65	Approved	[4]
Helminth infection	1F90.0	Approved	[4]
Trichuris trichiura infection	1F6G	Approved	[4]
Worm infection	1F90.Z	Approved	[5]

Mebendazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Binder	[20]

Mebendazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[21]

Mebendazole Interacts with 43 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[22]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Expression	[23]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[24]
L-lactate dehydrogenase A chain (LDHA)	OTN7K4XB	LDHA_HUMAN	Decreases Expression	[25]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[26]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[27]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[28]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[24]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[24]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[24]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Decreases Expression	[25]
Protein S100-A8 (S100A8)	OTVMOB3F	S10A8_HUMAN	Increases Expression	[29]
Protein S100-A9 (S100A9)	OTOARHCS	S10A9_HUMAN	Increases Expression	[29]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[30]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[24]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[19]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[28]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Phosphorylation	[31]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[32]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[25]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[19]
Hexokinase-1 (HK1)	OTMPHE8O	HXK1_HUMAN	Decreases Expression	[25]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[24]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[28]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[28]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Expression	[30]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[24]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[25]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[28]
Mitogen-activated protein kinase 9 (MAPK9)	OTCEVJ9E	MK09_HUMAN	Increases Phosphorylation	[28]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Decreases Expression	[33]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[25]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Decreases Expression	[34]
Ras-related C3 botulinum toxin substrate 1 (RAC1)	OTKRO61U	RAC1_HUMAN	Decreases Expression	[34]
Focal adhesion kinase 1 (PTK2)	OT3Q1JDY	FAK1_HUMAN	Decreases Expression	[34]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[24]
Transcription factor HES-1 (HES1)	OT8P19W2	HES1_HUMAN	Decreases Expression	[33]
Advanced glycosylation end product-specific receptor (AGER)	OTPY0IH7	RAGE_HUMAN	Increases Expression	[29]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[24]
Rho guanine nucleotide exchange factor 2 (ARHGEF2)	OTBQTFRT	ARHG2_HUMAN	Decreases Expression	[34]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Expression	[30]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[29]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[24]

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