Details of the Drug Combination

General Information of Drug Combination (ID: DCA8JCV)

• Drug Combination Name: Isoproterenol + Imipramine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Isoproterenol (DMK7MEY): Small molecular drug
  Imipramine (DM2NUH3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 17.29
  Bliss Independence Score: 17.29
  Loewe Additivity Score: 29.5
  LHighest Single Agent (HSA) Score: 29.5

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Isoproterenol

Disease Entry	ICD 11	Status	REF
Atrioventricular block	N.A.	Approved	[2]
Cardiac arrest	MC82	Approved	[2]
Common cold	CA00	Approved	[2]
Heart block	BC63	Approved	[3]
Melanoma	2C30	Phase 1	[4]

Isoproterenol Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Agonist	[8]
Adrenergic receptor beta-2 (ADRB2)	TT2CJVK	ADRB2_HUMAN	Modulator	[8]
Interleukin-12 beta (IL12B)	TTGW72V	IL12B_HUMAN	Modulator	[9]

Isoproterenol Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[10]

Isoproterenol Interacts with 74 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[11]
Apoptotic protease-activating factor 1 (APAF1)	OTJWIVY0	APAF_HUMAN	Increases Expression	[7]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Decreases Expression	[7]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[7]
Complement C3 (C3)	OTCH5GS0	CO3_HUMAN	Decreases Expression	[7]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Decreases Expression	[7]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[7]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Decreases Expression	[7]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[7]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[7]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[7]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[7]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[7]
Heat shock cognate 71 kDa protein (HSPA8)	OTJI2RCI	HSP7C_HUMAN	Decreases Expression	[7]
Interleukin-7 (IL7)	OTT6YSKM	IL7_HUMAN	Increases Expression	[7]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Decreases Expression	[7]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Expression	[7]
Caspase-1 (CASP1)	OTZ3YQFU	CASP1_HUMAN	Decreases Expression	[7]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Decreases Expression	[7]
Heat shock 70 kDa protein 1-like (HSPA1L)	OTC2V1K6	HS71L_HUMAN	Decreases Expression	[7]
Nitric oxide synthase, inducible (NOS2)	OTKKIOJ1	NOS2_HUMAN	Decreases Expression	[7]
Metalloproteinase inhibitor 3 (TIMP3)	OTDGQAD1	TIMP3_HUMAN	Increases Expression	[7]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Increases Expression	[7]
Heat shock-related 70 kDa protein 2 (HSPA2)	OTSDET7B	HSP72_HUMAN	Increases Expression	[7]
C-C motif chemokine 7 (CCL7)	OTDIS99H	CCL7_HUMAN	Decreases Expression	[7]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[7]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[7]
Four and a half LIM domains protein 1 (FHL1)	OTN535SU	FHL1_HUMAN	Decreases Expression	[7]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)	OTXEE550	APR_HUMAN	Increases Expression	[7]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Decreases Expression	[7]
Regenerating islet-derived protein 3-gamma (REG3G)	OTLIUY8Z	REG3G_HUMAN	Decreases Expression	[7]
Metalloproteinase inhibitor 4 (TIMP4)	OT8A68SW	TIMP4_HUMAN	Decreases Expression	[7]
Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2)	OTAQD3YV	ARNT2_HUMAN	Decreases Expression	[7]
Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN)	OT5LIL3W	HIF1N_HUMAN	Decreases Expression	[7]
Hypoxia-inducible factor 3-alpha (HIF3A)	OTPWAAMC	HIF3A_HUMAN	Increases Expression	[7]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[12]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Affects Binding	[13]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[14]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Expression	[15]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[16]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[17]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Secretion	[18]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[12]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Decreases Expression	[16]
Transferrin receptor protein 1 (TFRC)	OT8ZPBDL	TFR1_HUMAN	Decreases Expression	[19]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[12]
Alkaline phosphatase, placental type (ALPP)	OTZU4G9W	PPB1_HUMAN	Increases Expression	[20]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Expression	[21]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Increases Expression	[22]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[22]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Expression	[23]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[12]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Increases Activity	[24]
Beta-3 adrenergic receptor (ADRB3)	OTPMG4V7	ADRB3_HUMAN	Increases Activity	[25]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[26]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[17]
Beta-adrenergic receptor kinase 1 (GRK2)	OT34KKWK	ARBK1_HUMAN	Increases Expression	[27]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[28]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[28]
Beta-arrestin-2 (ARRB2)	OTAEJZCI	ARRB2_HUMAN	Affects Localization	[29]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[12]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Decreases Secretion	[30]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[12]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[12]
C-C motif chemokine 17 (CCL17)	OTIKW21L	CCL17_HUMAN	Decreases Secretion	[31]
Ryanodine receptor 2 (RYR2)	OT0PF19E	RYR2_HUMAN	Increases Phosphorylation	[32]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[12]
Interleukin-1 receptor antagonist protein (IL1RN)	OT308CBE	IL1RA_HUMAN	Affects Response To Substance	[33]
Dystroglycan 1 (DAG1)	OT6QBA05	DAG1_HUMAN	Increases ADR	[34]
Bone morphogenetic protein 10 (BMP10)	OTA3QKKG	BMP10_HUMAN	Decreases Response To Substance	[35]
Guanine nucleotide-binding protein G(olf) subunit alpha (GNAL)	OTESDTEU	GNAL_HUMAN	Increases Response To Substance	[36]
Neuroendocrine secretory protein 55 (GNAS)	OTMH8BKJ	GNAS3_HUMAN	Increases Response To Substance	[36]
Interleukin-5 receptor subunit alpha (IL5RA)	OTMSLUG9	IL5RA_HUMAN	Affects Response To Substance	[33]
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Methylation	[37]

Indication(s) of Imipramine

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[5]
Nocturia	MF55	Approved	[6]

Imipramine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[40]

Imipramine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[41]

Imipramine Interacts with 9 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[42]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[43]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[44]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[45]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[46]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[43]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[43]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[47]
Docosahexaenoic acid omega-hydroxylase (CYP4F11)	DEIZLTN	CP4FB_HUMAN	Metabolism	[48]

Imipramine Interacts with 32 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[49]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[38]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[38]
Serine protease hepsin (HPN)	OT7QNA61	HEPS_HUMAN	Increases Expression	[38]
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Increases Expression	[38]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[38]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Decreases Expression	[38]
Lanosterol synthase (LSS)	OT9W2SFH	LSS_HUMAN	Increases Expression	[38]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[38]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Decreases Expression	[38]
Acid ceramidase (ASAH1)	OT1DNGXL	ASAH1_HUMAN	Increases Expression	[38]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[38]
Lysophospholipase D GDPD3 (GDPD3)	OTOHM9QM	GDPD3_HUMAN	Increases Expression	[38]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[38]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[38]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[50]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[51]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Increases Expression	[52]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[53]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Decreases Expression	[54]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[55]
Alpha-1-acid glycoprotein 2 (ORM2)	OTRJGZP8	A1AG2_HUMAN	Affects Binding	[56]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[57]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[57]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Decreases Activity	[58]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[51]
Glutamate receptor ionotropic, NMDA 1 (GRIN1)	OTZ5YBO8	NMDZ1_HUMAN	Decreases Expression	[59]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[60]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Activity	[61]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[52]
DnaJ homolog subfamily C member 5 (DNAJC5)	OTCZDXAL	DNJC5_HUMAN	Increases Expression	[62]
SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)	OTSQTPFQ	SHAN2_HUMAN	Decreases Expression	[59]

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