Details of the Drug Combination

General Information of Drug Combination (ID: DCEFH87)

• Drug Combination Name: Bardoxolone methyl + Tamoxifen
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Bardoxolone methyl (DMODA2X): Small molecular drug
  Tamoxifen (DMLB0EZ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 22.569
  Bliss Independence Score: 23.895
  Loewe Additivity Score: 4.183
  LHighest Single Agent (HSA) Score: 5.591

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Bardoxolone methyl

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

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	[7]

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	[8]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[8]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[8]
Muscarinic acetylcholine receptor M2 (CHRM2)	OTUMZ2WR	ACM2_HUMAN	Decreases Activity	[9]
Muscarinic acetylcholine receptor M1 (CHRM1)	OTKW3E6B	ACM1_HUMAN	Decreases Activity	[9]
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Decreases Activity	[9]
Alpha-2C adrenergic receptor (ADRA2C)	OT5B9RKP	ADA2C_HUMAN	Decreases Activity	[9]
D(1A) dopamine receptor (DRD1)	OTLZPBT7	DRD1_HUMAN	Decreases Activity	[9]
Substance-P receptor (TACR1)	OTCL9OC5	NK1R_HUMAN	Decreases Activity	[9]
5-hydroxytryptamine receptor 2A (HTR2A)	OTWXJX0M	5HT2A_HUMAN	Decreases Activity	[9]
5-hydroxytryptamine receptor 2C (HTR2C)	OT6H8DE0	5HT2C_HUMAN	Decreases Activity	[9]
Histamine H1 receptor (HRH1)	OT8F9FV6	HRH1_HUMAN	Decreases Activity	[9]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Decreases Activity	[9]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Decreases Activity	[9]
Vasopressin V1a receptor (AVPR1A)	OTKR8AFL	V1AR_HUMAN	Decreases Activity	[9]
Kappa-type opioid receptor (OPRK1)	OTXCZF4L	OPRK_HUMAN	Decreases Activity	[9]
3',5'-cyclic-AMP phosphodiesterase 4B (PDE4B)	OTOA8WU2	PDE4B_HUMAN	Decreases Activity	[9]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Decreases Activity	[9]
Aurora kinase B (AURKB)	OTIY4VHU	AURKB_HUMAN	Decreases Activity	[9]
NF-kappa-B inhibitor epsilon (NFKBIE)	OTLAYEL9	IKBE_HUMAN	Increases Expression	[6]
Transcription factor MafG (MAFG)	OTBQFUZH	MAFG_HUMAN	Decreases Expression	[6]
SH3 domain-binding protein 5 (SH3BP5)	OTOOEGUJ	3BP5_HUMAN	Affects Expression	[10]
Dynamin-like 120 kDa protein, mitochondrial (OPA1)	OTJGNWPW	OPA1_HUMAN	Increases Cleavage	[11]
Mitofusin-2 (MFN2)	OTPYN8A3	MFN2_HUMAN	Decreases Expression	[11]
Urokinase-type plasminogen activator (PLAU)	OTX0QGKK	UROK_HUMAN	Increases Expression	[6]
Platelet-derived growth factor subunit B (PDGFB)	OTMFMFC3	PDGFB_HUMAN	Increases Expression	[6]
Annexin A1 (ANXA1)	OT5OFDJC	ANXA1_HUMAN	Affects Expression	[10]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Increases Expression	[6]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Decreases Expression	[6]
ATP-dependent 6-phosphofructokinase, muscle type (PFKM)	OT1QY9JM	PFKAM_HUMAN	Decreases Expression	[11]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Expression	[10]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Expression	[10]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Increases Expression	[6]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Expression	[6]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[12]
Retinoic acid receptor alpha (RARA)	OT192V9V	RARA_HUMAN	Affects Expression	[10]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[6]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[6]
Pyruvate kinase PKM (PKM)	OTLHHMC2	KPYM_HUMAN	Decreases Expression	[11]
Interleukin-1 receptor type 1 (IL1R1)	OTTU8959	IL1R1_HUMAN	Affects Expression	[10]
Beta-1,4-galactosyltransferase 1 (B4GALT1)	OTBCXEK7	B4GT1_HUMAN	Increases Expression	[6]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Decreases Expression	[6]
Glutathione peroxidase 2 (GPX2)	OTXI2NTI	GPX2_HUMAN	Affects Expression	[10]
C-X-C motif chemokine 2 (CXCL2)	OTEJCYMY	CXCL2_HUMAN	Increases Expression	[6]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)	OTVLI4DD	TNAP3_HUMAN	Increases Expression	[6]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[11]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Affects Expression	[10]
DnaJ homolog subfamily B member 1 (DNAJB1)	OTCOSEVH	DNJB1_HUMAN	Affects Expression	[10]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[6]
Lon protease homolog, mitochondrial (LONP1)	OT665WYT	LONM_HUMAN	Decreases Expression	[13]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Phosphorylation	[12]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[11]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Decreases Expression	[6]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Decreases Expression	[6]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Decreases Expression	[14]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Expression	[11]
Oxidized low-density lipoprotein receptor 1 (OLR1)	OTS44RIC	OLR1_HUMAN	Increases Expression	[6]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Increases Expression	[6]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[15]
Antigen peptide transporter 1 (TAP1)	OTJL27PW	TAP1_HUMAN	Increases Expression	[6]
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9)	OTNOM26L	TNR9_HUMAN	Increases Expression	[6]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Increases Expression	[6]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[6]
Kelch-like ECH-associated protein 1 (KEAP1)	OTFHOD0C	KEAP1_HUMAN	Decreases Expression	[6]
Neutral amino acid transporter B(0) (SLC1A5)	OTE2H26Q	AAAT_HUMAN	Decreases Expression	[11]
Mitofusin-1 (MFN1)	OTCBXQZF	MFN1_HUMAN	Decreases Expression	[11]
Scavenger receptor class B member 1 (SCARB1)	OTAE1UA1	SCRB1_HUMAN	Affects Expression	[10]
Thyroid hormone-inducible hepatic protein (THRSP)	OTKYE01L	THRSP_HUMAN	Decreases Expression	[14]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Increases Expression	[16]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[6]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Decreases Expression	[6]
Sigma non-opioid intracellular receptor 1 (SIGMAR1)	OTDORW5C	SGMR1_HUMAN	Decreases Expression	[13]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Decreases Expression	[6]
Prolyl hydroxylase EGLN3 (EGLN3)	OTXV3RYX	EGLN3_HUMAN	Affects Expression	[10]
5'-AMP-activated protein kinase subunit gamma-2 (PRKAG2)	OTHTAM54	AAKG2_HUMAN	Affects Expression	[6]

Indication(s) of Tamoxifen

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[4]
Inflammatory breast cancer	2C62	Approved	[5]
Invasive ductal breast carcinoma	N.A.	Approved	[5]

Tamoxifen Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Antagonist	[17]

Tamoxifen Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[18]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[19]
Multidrug resistance-associated protein 7 (ABCC10)	DTPS120	MRP7_HUMAN	Substrate	[20]

Tamoxifen Interacts with 16 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[21]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[22]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[23]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[24]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[25]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[26]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[27]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[28]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[24]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[29]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[30]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[31]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[32]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[33]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[34]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[35]

Tamoxifen Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Coagulation factor V (F5)	OTDMZ3LT	FA5_HUMAN	Increases ADR	[36]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Primitive neuroectodermal tumor	DCNDSRB	TC-32	Investigative	[1]

References

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