Details of the Drug Combination

General Information of Drug Combination (ID: DC2BNAX)

• Drug Combination Name: Methimazole + Propranolol
• Indication: Graves Disease; Status: Phase 4 [1]
• Component Drugs:
  Methimazole (DM25FL8): Small molecular drug
  Propranolol (DM79NTF): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Methimazole

Disease Entry	ICD 11	Status	REF
Hyperthyroidism	5A02	Approved	[2]

Methimazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Thyroid peroxidase (TPO)	TT52XDZ	PERT_HUMAN	Inhibitor	[6]

Methimazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Dimethylaniline oxidase 2 (FMO2)	DEIASEZ	FMO2_HUMAN	Metabolism	[7]

Methimazole Interacts with 43 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[8]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Increases Activity	[9]
T-box transcription factor TBX3 (TBX3)	OTM64N7K	TBX3_HUMAN	Increases Expression	[5]
Trans-Golgi network integral membrane protein 2 (TGOLN2)	OTM647IV	TGON2_HUMAN	Increases Expression	[5]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Increases Expression	[10]
Haptoglobin (HP)	OTGUGAF9	HPT_HUMAN	Increases Expression	[10]
Thyrotropin subunit beta (TSHB)	OTFDI39D	TSHB_HUMAN	Increases Expression	[11]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Decreases Expression	[12]
Alpha-fetoprotein (AFP)	OT9GG3ZI	FETA_HUMAN	Increases Expression	[12]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Decreases Expression	[12]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Decreases Expression	[12]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[10]
Thyroid peroxidase (TPO)	OTJJLL20	PERT_HUMAN	Decreases Activity	[13]
Insulin-like growth factor 1 receptor (IGF1R)	OTXJIF13	IGF1R_HUMAN	Decreases Expression	[12]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[10]
Microsomal glutathione S-transferase 1 (MGST1)	OTGN1KVZ	MGST1_HUMAN	Increases Expression	[10]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Decreases Expression	[12]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[5]
Thyrotropin receptor (TSHR)	OT0BC8LB	TSHR_HUMAN	Decreases Expression	[14]
Galectin-3 (LGALS3)	OTYQT0ZI	LEG3_HUMAN	Increases Expression	[10]
Integrin beta-5 (ITGB5)	OT21MF51	ITB5_HUMAN	Increases Expression	[5]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[12]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[12]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[12]
RAC-beta serine/threonine-protein kinase (AKT2)	OTBB632K	AKT2_HUMAN	Decreases Expression	[12]
Hepatocyte nuclear factor 4-alpha (HNF4A)	OTY1TOAB	HNF4A_HUMAN	Increases Expression	[12]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[12]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Increases Expression	[10]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Decreases Expression	[12]
Type I iodothyronine deiodinase (DIO1)	OTFYLYJ0	IOD1_HUMAN	Increases Expression	[14]
Hepcidin (HAMP)	OT607RBL	HEPC_HUMAN	Decreases Expression	[10]
Low-density lipoprotein receptor-related protein 2 (LRP2)	OTZ6W681	LRP2_HUMAN	Increases Expression	[14]
DNA-binding protein inhibitor ID-2 (ID2)	OT0U1D53	ID2_HUMAN	Increases Expression	[5]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Increases Expression	[5]
Krueppel-like factor 9 (KLF9)	OTBFEJRQ	KLF9_HUMAN	Increases Expression	[5]
Consortin (CNST)	OTOUCB98	CNST_HUMAN	Increases Expression	[5]
Sodium/iodide cotransporter (SLC5A5)	OTU7E9G7	SC5A5_HUMAN	Increases Expression	[14]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[15]
PTB domain-containing engulfment adapter protein 1 (GULP1)	OT1WMVDH	GULP1_HUMAN	Increases Expression	[5]
Flavin-containing monooxygenase 3 (FMO3)	OT1G2EV3	FMO3_HUMAN	Increases Metabolism	[16]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Increases Metabolism	[17]
Flavin-containing monooxygenase 1 (FMO1)	OTTHSQKP	FMO1_HUMAN	Increases Oxidation	[18]
Flavin-containing monooxygenase 2 (FMO2)	OTUJUL9S	FMO2_HUMAN	Decreases Oxidation	[19]

Indication(s) of Propranolol

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[3]
Atrial fibrillation	BC81.3	Approved	[3]
Cocaine addiction	6C45.2	Approved	[3]
Hemangioma	2E81-2F2Y	Approved	[3]
Migraine	8A80	Approved	[4]
Respiratory papillomatosis	2F00.1	Investigative	[3]

Propranolol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Antagonist	[21]

Propranolol Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[22]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[23]
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[23]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[23]

Propranolol Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[24]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[25]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[26]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[27]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[27]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[28]
Dimethylaniline oxidase 2 (FMO2)	DEIASEZ	FMO2_HUMAN	Metabolism	[29]
Cytochrome P450 102A1 (cyp102)	DE4OGUF	CPXB_BACMB	Metabolism	[30]

Propranolol Interacts with 34 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Oxidation	[31]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Oxidation	[31]
Flavin-containing monooxygenase 2 (FMO2)	OTUJUL9S	FMO2_HUMAN	Increases Oxidation	[29]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[32]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[33]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)	OT8SPJNX	KCNQ1_HUMAN	Affects Response To Substance	[34]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[20]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[20]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[20]
Angiopoietin-2 (ANGPT2)	OTEQK65P	ANGP2_HUMAN	Decreases Expression	[35]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[36]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[37]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Decreases Expression	[38]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[39]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Decreases Expression	[40]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[35]
Ornithine decarboxylase (ODC1)	OTNDAGRR	DCOR_HUMAN	Increases Activity	[41]
Beta-adrenergic receptor kinase 1 (GRK2)	OT34KKWK	ARBK1_HUMAN	Decreases Expression	[42]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[43]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[44]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[35]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Decreases Expression	[43]
G protein-activated inward rectifier potassium channel 1 (KCNJ3)	OTHQG16J	KCNJ3_HUMAN	Increases Expression	[40]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[44]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[45]
ADP-ribosylation factor 6 (ARF6)	OTVV7KJO	ARF6_HUMAN	Affects Localization	[46]
Angiopoietin-1 receptor (TEK)	OT78YN57	TIE2_HUMAN	Decreases Expression	[35]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[35]
Delta-like protein 4 (DLL4)	OTRA4K2V	DLL4_HUMAN	Decreases Expression	[43]
Inward rectifier potassium channel 2 (KCNJ2)	OT2OQEZS	KCNJ2_HUMAN	Affects Response To Substance	[34]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases ADR	[47]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Increases Oxidation	[31]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Increases ADR	[47]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases ADR	[47]

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