Details of the Drug Combination

General Information of Drug Combination (ID: DCBJVJS)

• Drug Combination Name: MK-2206 + Mebendazole
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  MK-2206 (DMT1OZ6): Small molecular drug
  Mebendazole (DMO14SG): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DIPG25
  Zero Interaction Potency (ZIP) Score: 4.08
  Bliss Independence Score: 1.78
  Loewe Additivity Score: 8.41
  LHighest Single Agent (HSA) Score: 9.51

Molecular Interaction Atlas of This Drug Combination

Indication(s) of MK-2206

Disease Entry	ICD 11	Status	REF
Rectal adenocarcinoma	2B92	Phase 2	[2]
Nasopharyngeal carcinoma	2B6B	Investigative	[3]

MK-2206 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RAC-gamma serine/threonine-protein kinase (AKT3)	TTAZ05C	AKT3_HUMAN	Modulator	[7]
E2 ubiquitin-conjugating enzyme T (UBE2T)	TT0A1R8	UBE2T_HUMAN	Inhibitor	[3]

MK-2206 Interacts with 20 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Expression	[8]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[6]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Expression	[8]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[6]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[6]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[9]
Vascular endothelial growth factor receptor 1 (FLT1)	OTT0OGYS	VGFR1_HUMAN	Decreases Expression	[6]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[6]
Endothelin receptor type B (EDNRB)	OTLLZV3P	EDNRB_HUMAN	Increases Expression	[6]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Affects Response To Substance	[10]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[11]
T-lymphocyte activation antigen CD80 (CD80)	OTJBLUQE	CD80_HUMAN	Decreases Expression	[6]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[6]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[11]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Decreases Expression	[6]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Decreases Expression	[12]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[11]
Interferon regulatory factor 8 (IRF8)	OT8YSNI4	IRF8_HUMAN	Decreases Expression	[6]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[11]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Phosphorylation	[13]

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	[15]

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	[16]

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	[17]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Expression	[18]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[19]
L-lactate dehydrogenase A chain (LDHA)	OTN7K4XB	LDHA_HUMAN	Decreases Expression	[20]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[21]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[22]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[23]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[19]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[19]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[19]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Decreases Expression	[20]
Protein S100-A8 (S100A8)	OTVMOB3F	S10A8_HUMAN	Increases Expression	[24]
Protein S100-A9 (S100A9)	OTOARHCS	S10A9_HUMAN	Increases Expression	[24]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[25]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[19]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[14]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[23]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Phosphorylation	[26]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[27]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[20]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[14]
Hexokinase-1 (HK1)	OTMPHE8O	HXK1_HUMAN	Decreases Expression	[20]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[19]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[23]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[23]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Expression	[25]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[19]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[20]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[23]
Mitogen-activated protein kinase 9 (MAPK9)	OTCEVJ9E	MK09_HUMAN	Increases Phosphorylation	[23]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Decreases Expression	[28]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[20]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Decreases Expression	[29]
Ras-related C3 botulinum toxin substrate 1 (RAC1)	OTKRO61U	RAC1_HUMAN	Decreases Expression	[29]
Focal adhesion kinase 1 (PTK2)	OT3Q1JDY	FAK1_HUMAN	Decreases Expression	[29]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[19]
Transcription factor HES-1 (HES1)	OT8P19W2	HES1_HUMAN	Decreases Expression	[28]
Advanced glycosylation end product-specific receptor (AGER)	OTPY0IH7	RAGE_HUMAN	Increases Expression	[24]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[19]
Rho guanine nucleotide exchange factor 2 (ARHGEF2)	OTBQTFRT	ARHG2_HUMAN	Decreases Expression	[29]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Expression	[25]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[24]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[19]

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