Details of the Drug Combination

General Information of Drug Combination (ID: DC5ZXBW)

• Drug Combination Name: Cilostazol + Epinephrine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Cilostazol (DMZMSCT): Small molecular drug
  Epinephrine (DM3KJBC): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 5.46
  Bliss Independence Score: 5.46
  Loewe Additivity Score: 7.01
  LHighest Single Agent (HSA) Score: 7.02

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cilostazol

Disease Entry	ICD 11	Status	REF
Intermittent claudication	BD40.00	Approved	[2]

Cilostazol Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Modulator	[5]
Phosphodiesterase 3A (PDE3A)	TT06AWU	PDE3A_HUMAN	Inhibitor	[6]

Cilostazol Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[7]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[7]

Cilostazol Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[9]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[9]

Cilostazol Interacts with 20 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Increases Localization	[10]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Response To Substance	[11]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[12]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[10]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[10]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Decreases Expression	[13]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Increases Activity	[14]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[13]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[10]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Phosphorylation	[15]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[15]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Increases Activity	[11]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[12]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[10]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[16]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[13]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[16]
Transcription factor E2F2 (E2F2)	OTO75RM7	E2F2_HUMAN	Decreases Expression	[13]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[10]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Increases Expression	[15]

Indication(s) of Epinephrine

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[3]
Allergy	4A80-4A85	Approved	[4]
Anaphylaxis	N.A.	Approved	[3]
Bronchiectasis	CA24	Approved	[3]
Bronchitis	CA20	Approved	[3]
Periodontitis	DA0C	Approved	[3]
Pulmonary emphysema	CA21.Z	Approved	[3]
Severe asthma	CA23	Approved	[3]
Asthma	CA23	Investigative	[3]

Epinephrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Agonist	[17]

Epinephrine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[18]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[19]

Epinephrine Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[20]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[21]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[22]
Catechol O-methyltransferase (COMT)	DEV3T4A	COMT_HUMAN	Metabolism	[23]
Monoamine oxidase type A (MAO-A)	DERE4TU	AOFA_HUMAN	Metabolism	[24]

Epinephrine Interacts with 33 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Methylation	[25]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[26]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[27]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[27]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Increases Expression	[28]
Integrin alpha-V (ITGAV)	OTAM7JTR	ITAV_HUMAN	Increases Expression	[28]
Cathepsin K (CTSK)	OTT3YX5O	CATK_HUMAN	Increases Expression	[28]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[29]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[30]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Activity	[31]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Cleavage	[32]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[32]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Increases Expression	[32]
Pyruvate kinase PKM (PKM)	OTLHHMC2	KPYM_HUMAN	Increases Expression	[32]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Activity	[33]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[34]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Increases Activity	[33]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Increases Activity	[33]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[34]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[34]
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Increases Expression	[32]
Ephrin type-A receptor 4 (EPHA4)	OT3AMK0C	EPHA4_HUMAN	Increases Phosphorylation	[35]
Hormone-sensitive lipase (LIPE)	OTMMVJ8A	LIPS_HUMAN	Increases Activity	[36]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[32]
P2X purinoceptor 7 (P2RX7)	OTNJ9XPL	P2RX7_HUMAN	Decreases Activity	[37]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases ADR	[38]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Response To Substance	[39]
Sulfotransferase 1A3 (SULT1A4)	OTHJ8WWV	ST1A3_HUMAN	Increases Sulfation	[40]
Glutathione reductase, mitochondrial (GSR)	OTM2TUYM	GSHR_HUMAN	Increases ADR	[38]
Neuron-specific vesicular protein calcyon (CALY)	OTQ7EMPU	CALY_HUMAN	Decreases Secretion	[41]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases ADR	[38]
Equilibrative nucleoside transporter 4 (SLC29A4)	OTWTZXMX	S29A4_HUMAN	Increases Uptake	[26]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Increases ADR	[38]

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