General Information of Drug Combination (ID: DCBOAE9)

Drug Combination Name
Terazosin Isoproterenol
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Terazosin   DM3JCVS Isoproterenol   DMK7MEY
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 0.3
Bliss Independence Score: 0.3
Loewe Additivity Score: 15.94
LHighest Single Agent (HSA) Score: 15.94

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Terazosin
Disease Entry ICD 11 Status REF
Benign prostatic hyperplasia GA90 Approved [2]
Terazosin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor alpha-1D (ADRA1D) TT34BHT ADA1D_HUMAN Antagonist [6]
------------------------------------------------------------------------------------
Indication(s) of Isoproterenol
Disease Entry ICD 11 Status REF
Atrioventricular block N.A. Approved [3]
Cardiac arrest MC82 Approved [3]
Common cold CA00 Approved [3]
Heart block BC63 Approved [4]
Melanoma 2C30 Phase 1 [5]
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]
------------------------------------------------------------------------------------
⏷ Show the Full List of 74 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7302).
3 Isoproterenol FDA Label
4 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 083346.
5 A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma. Clin Cancer Res. 2011 Apr 1;17(7):1998-2005.
6 Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
7 Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo. Toxicol Appl Pharmacol. 2014 Jan 15;274(2):302-12.
8 Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists. Eur J Clin Pharmacol. 1998 Feb;53(6):389-404.
9 A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma. Clin Cancer Res. 2011 Apr 1;17(7):1998-2005.
10 Identification, characterization, and ontogenic study of a catechol O-methyltransferase from zebrafish. Aquat Toxicol. 2011 Mar;102(1-2):18-23.
11 Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87.
12 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
13 Ligand binding and aggregation of pathogenic SOD1. Nat Commun. 2013;4:1758. doi: 10.1038/ncomms2750.
14 Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med. 1983 Dec 8;309(23):1414-9. doi: 10.1056/NEJM198312083092303.
15 Vascular renin-angiotensin system and neurotransmission in hypertensive persons. Hypertension. 1991 Sep;18(3):266-77. doi: 10.1161/01.hyp.18.3.266.
16 The regulation of human vascular smooth muscle extracellular matrix protein production by alpha- and beta-adrenoceptor stimulation. J Hypertens. 2002 Feb;20(2):287-94. doi: 10.1097/00004872-200202000-00019.
17 Low doses of BPF-induced hypertrophy in cardiomyocytes derived from human embryonic stem cells via disrupting the mitochondrial fission upon the interaction between ER and calcineurin A-DRP1 signaling pathway. Cell Biol Toxicol. 2022 Jun;38(3):409-426. doi: 10.1007/s10565-021-09615-y. Epub 2021 May 22.
18 Post-receptorial mechanisms underlie functional disregulation of beta2-adrenergic receptors in lymphocytes from Multiple Sclerosis patients. J Neuroimmunol. 2004 Oct;155(1-2):143-9. doi: 10.1016/j.jneuroim.2004.05.013.
19 Prostaglandin E2 acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down-regulation of transferrin receptor expression. J Immunol. 1985 Aug;135(2):1172-9.
20 The effects of desmethylimipramine on cyclic AMP-stimulated gene transcription in a model cell system. Biochem Pharmacol. 2005 Sep 1;70(5):762-9. doi: 10.1016/j.bcp.2005.06.012.
21 Isoproterenol inhibits angiotensin II-stimulated proliferation and reactive oxygen species production in vascular smooth muscle cells through heme oxygenase-1. Biol Pharm Bull. 2009 Jun;32(6):1047-52. doi: 10.1248/bpb.32.1047.
22 Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of MDA-MB-231 human breast cancer cells by blocking ?-adrenergic signaling. Arch Biochem Biophys. 2014 Sep 1;557:18-27. doi: 10.1016/j.abb.2014.05.030. Epub 2014 Jun 11.
23 Impaired PARP activity in response to the -adrenergic receptor agonist isoproterenol. Toxicol In Vitro. 2018 Aug;50:29-39. doi: 10.1016/j.tiv.2018.02.001. Epub 2018 Feb 10.
24 Activation of airway cl- secretion in human subjects by adenosine. Am J Respir Cell Mol Biol. 2004 Aug;31(2):140-6. doi: 10.1165/rcmb.2004-0012OC. Epub 2004 Mar 23.
25 Discovery of a novel series of biphenyl benzoic acid derivatives as highly potent and selective human beta3 adrenergic receptor agonists with good oral bioavailability. Part II. J Med Chem. 2008 Jul 10;51(13):4002-20. doi: 10.1021/jm8000345. Epub 2008 Jun 14.
26 Adrenoceptor blockade alters plasma gelatinase activity in patients with heart failure and MMP-9 promoter activity in a human cell line (ECV304). Pharmacol Res. 2006 Jul;54(1):57-64. doi: 10.1016/j.phrs.2006.02.006. Epub 2006 Feb 28.
27 Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade. Circulation. 1998 Oct 27;98(17):1783-9. doi: 10.1161/01.cir.98.17.1783.
28 A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
29 Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell. 2007 May 4;129(3):511-22. doi: 10.1016/j.cell.2007.02.046.
30 Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes in primary culture via beta1- and beta2-adrenergic receptors. Eur J Endocrinol. 2000 Sep;143(3):439-45. doi: 10.1530/eje.0.1430439.
31 IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype. Am J Physiol Lung Cell Mol Physiol. 2003 Oct;285(4):L907-14. doi: 10.1152/ajplung.00120.2003. Epub 2003 Jul 18.
32 Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2+ release. Nat Med. 2011 Jul 10;17(8):1003-9. doi: 10.1038/nm.2406.
33 Autocrine interaction between IL-5 and IL-1beta mediates altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J Clin Invest. 1999 Sep;104(5):657-67. doi: 10.1172/JCI7137.
34 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
35 BMP10 preserves cardiac function through its dual activation of SMAD-mediated and STAT3-mediated pathways. J Biol Chem. 2019 Dec 27;294(52):19877-19888. doi: 10.1074/jbc.RA119.010943. Epub 2019 Nov 11.
36 Identification of specific ligands for orphan olfactory receptors. G protein-dependent agonism and antagonism of odorants. J Biol Chem. 2005 Mar 25;280(12):11807-15. doi: 10.1074/jbc.M411508200. Epub 2004 Dec 14.
37 Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase. Mol Pharmacol. 2001 Feb;59(2):393-402. doi: 10.1124/mol.59.2.393.