General Information of Drug Combination (ID: DCEHXCS)

Drug Combination Name
Pargyline Isoproterenol
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Pargyline   DMM0HR1 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: 27.78
Bliss Independence Score: 27.78
Loewe Additivity Score: 40.14
LHighest Single Agent (HSA) Score: 40.14

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Pargyline
Disease Entry ICD 11 Status REF
Hypertension BA00-BA04 Approved [2]
Muscular dystrophy 8C70 Patented [3]
Skin imperfections EK71 Patented [3]
Pargyline Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Monoamine oxidase (MAO) TT32XQJ NOUNIPROTAC Inhibitor [3]
Monoamine oxidase type B (MAO-B) TTGP7BY AOFB_HUMAN Inhibitor [7]
------------------------------------------------------------------------------------
Pargyline Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Decreases Activity [8]
Amine oxidase B (MAOB) OTTDFM1O AOFB_HUMAN Decreases Activity [9]
------------------------------------------------------------------------------------
Indication(s) of Isoproterenol
Disease Entry ICD 11 Status REF
Atrioventricular block N.A. Approved [4]
Cardiac arrest MC82 Approved [4]
Common cold CA00 Approved [4]
Heart block BC63 Approved [5]
Melanoma 2C30 Phase 1 [6]
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 [11]
Adrenergic receptor beta-2 (ADRB2) TT2CJVK ADRB2_HUMAN Modulator [11]
Interleukin-12 beta (IL12B) TTGW72V IL12B_HUMAN Modulator [12]
------------------------------------------------------------------------------------
Isoproterenol Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [13]
------------------------------------------------------------------------------------
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 [14]
Apoptotic protease-activating factor 1 (APAF1) OTJWIVY0 APAF_HUMAN Increases Expression [10]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Decreases Expression [10]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [10]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Decreases Expression [10]
Metalloproteinase inhibitor 1 (TIMP1) OTOXC51H TIMP1_HUMAN Decreases Expression [10]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Expression [10]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Decreases Expression [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Decreases Expression [10]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [10]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [10]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Increases Expression [10]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Decreases Expression [10]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Decreases Expression [10]
Interleukin-7 (IL7) OTT6YSKM IL7_HUMAN Increases Expression [10]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [10]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Expression [10]
Caspase-1 (CASP1) OTZ3YQFU CASP1_HUMAN Decreases Expression [10]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Decreases Expression [10]
Heat shock 70 kDa protein 1-like (HSPA1L) OTC2V1K6 HS71L_HUMAN Decreases Expression [10]
Nitric oxide synthase, inducible (NOS2) OTKKIOJ1 NOS2_HUMAN Decreases Expression [10]
Metalloproteinase inhibitor 3 (TIMP3) OTDGQAD1 TIMP3_HUMAN Increases Expression [10]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [10]
Heat shock-related 70 kDa protein 2 (HSPA2) OTSDET7B HSP72_HUMAN Increases Expression [10]
C-C motif chemokine 7 (CCL7) OTDIS99H CCL7_HUMAN Decreases Expression [10]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Decreases Expression [10]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [10]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Decreases Expression [10]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Increases Expression [10]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Decreases Expression [10]
Regenerating islet-derived protein 3-gamma (REG3G) OTLIUY8Z REG3G_HUMAN Decreases Expression [10]
Metalloproteinase inhibitor 4 (TIMP4) OT8A68SW TIMP4_HUMAN Decreases Expression [10]
Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) OTAQD3YV ARNT2_HUMAN Decreases Expression [10]
Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN) OT5LIL3W HIF1N_HUMAN Decreases Expression [10]
Hypoxia-inducible factor 3-alpha (HIF3A) OTPWAAMC HIF3A_HUMAN Increases Expression [10]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [15]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Affects Binding [16]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [17]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [18]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Expression [19]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases Expression [20]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Decreases Secretion [21]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [15]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Decreases Expression [19]
Transferrin receptor protein 1 (TFRC) OT8ZPBDL TFR1_HUMAN Decreases Expression [22]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [15]
Alkaline phosphatase, placental type (ALPP) OTZU4G9W PPB1_HUMAN Increases Expression [23]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Expression [24]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Increases Expression [25]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [25]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Expression [26]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [15]
Cystic fibrosis transmembrane conductance regulator (CFTR) OT6B22QH CFTR_HUMAN Increases Activity [27]
Beta-3 adrenergic receptor (ADRB3) OTPMG4V7 ADRB3_HUMAN Increases Activity [28]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Increases Expression [29]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [20]
Beta-adrenergic receptor kinase 1 (GRK2) OT34KKWK ARBK1_HUMAN Increases Expression [30]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [31]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [31]
Beta-arrestin-2 (ARRB2) OTAEJZCI ARRB2_HUMAN Affects Localization [32]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [15]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Decreases Secretion [33]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Decreases Expression [15]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [15]
C-C motif chemokine 17 (CCL17) OTIKW21L CCL17_HUMAN Decreases Secretion [34]
Ryanodine receptor 2 (RYR2) OT0PF19E RYR2_HUMAN Increases Phosphorylation [35]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Increases Expression [15]
Interleukin-1 receptor antagonist protein (IL1RN) OT308CBE IL1RA_HUMAN Affects Response To Substance [36]
Dystroglycan 1 (DAG1) OT6QBA05 DAG1_HUMAN Increases ADR [37]
Bone morphogenetic protein 10 (BMP10) OTA3QKKG BMP10_HUMAN Decreases Response To Substance [38]
Guanine nucleotide-binding protein G(olf) subunit alpha (GNAL) OTESDTEU GNAL_HUMAN Increases Response To Substance [39]
Neuroendocrine secretory protein 55 (GNAS) OTMH8BKJ GNAS3_HUMAN Increases Response To Substance [39]
Interleukin-5 receptor subunit alpha (IL5RA) OTMSLUG9 IL5RA_HUMAN Affects Response To Substance [36]
Catechol O-methyltransferase (COMT) OTPWKTQG COMT_HUMAN Increases Methylation [40]
------------------------------------------------------------------------------------
⏷ 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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
4 Isoproterenol FDA Label
5 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 083346.
6 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.
7 Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
8 Evaluation of metabolism dependent inhibition of CYP2B6 mediated bupropion hydroxylation in human liver microsomes by monoamine oxidase inhibitors and prediction of potential as perpetrators of drug interaction. Chem Biol Interact. 2015 Mar 25;230:9-20.
9 Combining initro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. Chem Biol Interact. 2016 Jul 25;254:135-45.
10 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.
11 Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists. Eur J Clin Pharmacol. 1998 Feb;53(6):389-404.
12 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.
13 Identification, characterization, and ontogenic study of a catechol O-methyltransferase from zebrafish. Aquat Toxicol. 2011 Mar;102(1-2):18-23.
14 Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87.
15 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.
16 Ligand binding and aggregation of pathogenic SOD1. Nat Commun. 2013;4:1758. doi: 10.1038/ncomms2750.
17 Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med. 1983 Dec 8;309(23):1414-9. doi: 10.1056/NEJM198312083092303.
18 Vascular renin-angiotensin system and neurotransmission in hypertensive persons. Hypertension. 1991 Sep;18(3):266-77. doi: 10.1161/01.hyp.18.3.266.
19 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.
20 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.
21 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.
22 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.
23 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.
24 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.
25 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.
26 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.
27 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.
28 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.
29 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.
30 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.
31 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.
32 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.
33 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.
34 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.
35 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.
36 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.
37 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.
38 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.
39 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.
40 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.