Details of the Drug Combination

General Information of Drug Combination (ID: DC4LR26)

• Drug Combination Name: MK-2206 + Bardoxolone methyl
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  MK-2206 (DMT1OZ6): Small molecular drug
  Bardoxolone methyl (DMODA2X): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: U-HO1
  Zero Interaction Potency (ZIP) Score: 0.43
  Bliss Independence Score: 2.59
  Loewe Additivity Score: 0.39
  LHighest Single Agent (HSA) Score: 3.61

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 Bardoxolone methyl

Disease Entry	ICD 11	Status	REF
Mixed connective tissue disease	4A43.3	Phase 3	[4]
Pulmonary arterial hypertension	BB01.0	Phase 2	[5]
Pulmonary hypertension	BB01	Phase 2	[4]

Bardoxolone methyl Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
PPAR-gamma messenger RNA (PPARG mRNA)	TTT2SVW	PPARG_HUMAN	Antagonist	[15]

Bardoxolone methyl Interacts with 75 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Increases Phosphorylation	[16]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[16]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[16]
Muscarinic acetylcholine receptor M2 (CHRM2)	OTUMZ2WR	ACM2_HUMAN	Decreases Activity	[17]
Muscarinic acetylcholine receptor M1 (CHRM1)	OTKW3E6B	ACM1_HUMAN	Decreases Activity	[17]
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Decreases Activity	[17]
Alpha-2C adrenergic receptor (ADRA2C)	OT5B9RKP	ADA2C_HUMAN	Decreases Activity	[17]
D(1A) dopamine receptor (DRD1)	OTLZPBT7	DRD1_HUMAN	Decreases Activity	[17]
Substance-P receptor (TACR1)	OTCL9OC5	NK1R_HUMAN	Decreases Activity	[17]
5-hydroxytryptamine receptor 2A (HTR2A)	OTWXJX0M	5HT2A_HUMAN	Decreases Activity	[17]
5-hydroxytryptamine receptor 2C (HTR2C)	OT6H8DE0	5HT2C_HUMAN	Decreases Activity	[17]
Histamine H1 receptor (HRH1)	OT8F9FV6	HRH1_HUMAN	Decreases Activity	[17]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Decreases Activity	[17]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Decreases Activity	[17]
Vasopressin V1a receptor (AVPR1A)	OTKR8AFL	V1AR_HUMAN	Decreases Activity	[17]
Kappa-type opioid receptor (OPRK1)	OTXCZF4L	OPRK_HUMAN	Decreases Activity	[17]
3',5'-cyclic-AMP phosphodiesterase 4B (PDE4B)	OTOA8WU2	PDE4B_HUMAN	Decreases Activity	[17]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Decreases Activity	[17]
Aurora kinase B (AURKB)	OTIY4VHU	AURKB_HUMAN	Decreases Activity	[17]
NF-kappa-B inhibitor epsilon (NFKBIE)	OTLAYEL9	IKBE_HUMAN	Increases Expression	[14]
Transcription factor MafG (MAFG)	OTBQFUZH	MAFG_HUMAN	Decreases Expression	[14]
SH3 domain-binding protein 5 (SH3BP5)	OTOOEGUJ	3BP5_HUMAN	Affects Expression	[18]
Dynamin-like 120 kDa protein, mitochondrial (OPA1)	OTJGNWPW	OPA1_HUMAN	Increases Cleavage	[19]
Mitofusin-2 (MFN2)	OTPYN8A3	MFN2_HUMAN	Decreases Expression	[19]
Urokinase-type plasminogen activator (PLAU)	OTX0QGKK	UROK_HUMAN	Increases Expression	[14]
Platelet-derived growth factor subunit B (PDGFB)	OTMFMFC3	PDGFB_HUMAN	Increases Expression	[14]
Annexin A1 (ANXA1)	OT5OFDJC	ANXA1_HUMAN	Affects Expression	[18]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Increases Expression	[14]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Decreases Expression	[14]
ATP-dependent 6-phosphofructokinase, muscle type (PFKM)	OT1QY9JM	PFKAM_HUMAN	Decreases Expression	[19]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Expression	[18]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Expression	[18]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Increases Expression	[14]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Expression	[14]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[20]
Retinoic acid receptor alpha (RARA)	OT192V9V	RARA_HUMAN	Affects Expression	[18]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[14]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[14]
Pyruvate kinase PKM (PKM)	OTLHHMC2	KPYM_HUMAN	Decreases Expression	[19]
Interleukin-1 receptor type 1 (IL1R1)	OTTU8959	IL1R1_HUMAN	Affects Expression	[18]
Beta-1,4-galactosyltransferase 1 (B4GALT1)	OTBCXEK7	B4GT1_HUMAN	Increases Expression	[14]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Decreases Expression	[14]
Glutathione peroxidase 2 (GPX2)	OTXI2NTI	GPX2_HUMAN	Affects Expression	[18]
C-X-C motif chemokine 2 (CXCL2)	OTEJCYMY	CXCL2_HUMAN	Increases Expression	[14]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)	OTVLI4DD	TNAP3_HUMAN	Increases Expression	[14]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[19]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Affects Expression	[18]
DnaJ homolog subfamily B member 1 (DNAJB1)	OTCOSEVH	DNJB1_HUMAN	Affects Expression	[18]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[14]
Lon protease homolog, mitochondrial (LONP1)	OT665WYT	LONM_HUMAN	Decreases Expression	[21]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Phosphorylation	[20]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[19]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Decreases Expression	[14]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Decreases Expression	[14]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Decreases Expression	[22]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Expression	[19]
Oxidized low-density lipoprotein receptor 1 (OLR1)	OTS44RIC	OLR1_HUMAN	Increases Expression	[14]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Increases Expression	[14]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[23]
Antigen peptide transporter 1 (TAP1)	OTJL27PW	TAP1_HUMAN	Increases Expression	[14]
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9)	OTNOM26L	TNR9_HUMAN	Increases Expression	[14]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Increases Expression	[14]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[14]
Kelch-like ECH-associated protein 1 (KEAP1)	OTFHOD0C	KEAP1_HUMAN	Decreases Expression	[14]
Neutral amino acid transporter B(0) (SLC1A5)	OTE2H26Q	AAAT_HUMAN	Decreases Expression	[19]
Mitofusin-1 (MFN1)	OTCBXQZF	MFN1_HUMAN	Decreases Expression	[19]
Scavenger receptor class B member 1 (SCARB1)	OTAE1UA1	SCRB1_HUMAN	Affects Expression	[18]
Thyroid hormone-inducible hepatic protein (THRSP)	OTKYE01L	THRSP_HUMAN	Decreases Expression	[22]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Increases Expression	[24]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[14]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Decreases Expression	[14]
Sigma non-opioid intracellular receptor 1 (SIGMAR1)	OTDORW5C	SGMR1_HUMAN	Decreases Expression	[21]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Decreases Expression	[14]
Prolyl hydroxylase EGLN3 (EGLN3)	OTXV3RYX	EGLN3_HUMAN	Affects Expression	[18]
5'-AMP-activated protein kinase subunit gamma-2 (PRKAG2)	OTHTAM54	AAKG2_HUMAN	Affects Expression	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Ewing sarcoma	DC148H3	TC-71	Investigative	[1]

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