General Information of Drug Combination (ID: DCGFI6O)

Drug Combination Name
Pizotyline Epinephrine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Pizotyline   DMV74ZH Epinephrine   DM3KJBC
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: 6.01
Bliss Independence Score: 6.01
Loewe Additivity Score: 7.53
LHighest Single Agent (HSA) Score: 7.53

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Pizotyline
Disease Entry ICD 11 Status REF
Headache 8A80-8A84 Approved [2]
Pizotyline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
5-HT receptor (5HTR) TT85JO3 NOUNIPROTAC Modulator [5]
------------------------------------------------------------------------------------
Pizotyline Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 2B10 (UGT2B10) DEI8NGH UDB10_HUMAN Metabolism [6]
------------------------------------------------------------------------------------
Pizotyline Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [7]
------------------------------------------------------------------------------------
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 [8]
------------------------------------------------------------------------------------
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 [9]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [10]
------------------------------------------------------------------------------------
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 [11]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Metabolism [12]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [13]
Catechol O-methyltransferase (COMT) DEV3T4A COMT_HUMAN Metabolism [14]
Monoamine oxidase type A (MAO-A) DERE4TU AOFA_HUMAN Metabolism [15]
------------------------------------------------------------------------------------
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 [16]
Solute carrier family 22 member 3 (SLC22A3) OTQYGVXX S22A3_HUMAN Increases Uptake [17]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Increases Expression [18]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [18]
Carbonic anhydrase 2 (CA2) OTJRMUAG CAH2_HUMAN Increases Expression [19]
Integrin alpha-V (ITGAV) OTAM7JTR ITAV_HUMAN Increases Expression [19]
Cathepsin K (CTSK) OTT3YX5O CATK_HUMAN Increases Expression [19]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [20]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [21]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Activity [22]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Cleavage [23]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [23]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Increases Expression [23]
Pyruvate kinase PKM (PKM) OTLHHMC2 KPYM_HUMAN Increases Expression [23]
Alpha-1D adrenergic receptor (ADRA1D) OTW2CD1O ADA1D_HUMAN Increases Activity [24]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [25]
Alpha-1A adrenergic receptor (ADRA1A) OTUIWCL5 ADA1A_HUMAN Increases Activity [24]
Alpha-1B adrenergic receptor (ADRA1B) OTSAYAFD ADA1B_HUMAN Increases Activity [24]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [25]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [25]
Hexokinase-2 (HK2) OTC0GCQO HXK2_HUMAN Increases Expression [23]
Ephrin type-A receptor 4 (EPHA4) OT3AMK0C EPHA4_HUMAN Increases Phosphorylation [26]
Hormone-sensitive lipase (LIPE) OTMMVJ8A LIPS_HUMAN Increases Activity [27]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [23]
P2X purinoceptor 7 (P2RX7) OTNJ9XPL P2RX7_HUMAN Decreases Activity [28]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Increases ADR [29]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Response To Substance [30]
Sulfotransferase 1A3 (SULT1A4) OTHJ8WWV ST1A3_HUMAN Increases Sulfation [31]
Glutathione reductase, mitochondrial (GSR) OTM2TUYM GSHR_HUMAN Increases ADR [29]
Neuron-specific vesicular protein calcyon (CALY) OTQ7EMPU CALY_HUMAN Decreases Secretion [32]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases ADR [29]
Equilibrative nucleoside transporter 4 (SLC29A4) OTWTZXMX S29A4_HUMAN Increases Uptake [17]
Alpha-2A adrenergic receptor (ADRA2A) OTZFGOTP ADA2A_HUMAN Increases ADR [29]
------------------------------------------------------------------------------------
⏷ Show the Full List of 33 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: 93).
3 Epinephrine FDA Label
4 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: 509).
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97.
7 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
8 Adrenergic activation of electrogenic K+ secretion in guinea pig distal colonic epithelium: involvement of beta1- and beta2-adrenergic receptors. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G269-77.
9 Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
10 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
11 Steroid glucuronides: human circulatory levels and formation by LNCaP cells. J Steroid Biochem Mol Biol. 1991;40(4-6):593-8.
12 Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate. Biochem Biophys Res Commun. 2005 Sep 23;335(2):417-23.
13 Adrenal catecholamines and their metabolism in the vitamin A deficient rat. Ann Nutr Metab. 1983;27(3):220-7.
14 Different metabolism of norepinephrine and epinephrine by catechol-O-methyltransferase and monoamine oxidase in rats. J Pharmacol Exp Ther. 1994 Mar;268(3):1242-51.
15 Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study. J Neurooncol. 2019 Nov;145(2):287-294.
16 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.
17 Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3. J Pharmacol Exp Ther. 2010 Dec;335(3):743-53. doi: 10.1124/jpet.110.170142. Epub 2010 Sep 21.
18 Epinephrine upregulates superoxide dismutase in human coronary artery endothelial cells. Free Radic Biol Med. 2001 Jan 15;30(2):148-53.
19 Effects of beta-adrenergic agonists on bone-resorbing activity in human osteoclast-like cells. Biochim Biophys Acta. 2003 May 12;1640(2-3):137-42.
20 Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med. 1983 Dec 8;309(23):1414-9. doi: 10.1056/NEJM198312083092303.
21 A receptor mechanism for the inhibition of insulin release by epinephrine in man. J Clin Invest. 1967 Jan;46(1):86-94. doi: 10.1172/JCI105514.
22 Myocardial ischaemia and ventricular arrhthymias precipitated by physiological concentrations of adrenaline in patients with coronary artery disease. Br Heart J. 1992 May;67(5):419-20. doi: 10.1136/hrt.67.5.419-b.
23 Epinephrine facilitates the growth of T cell lymphoma by altering cell proliferation, apoptosis, and glucose metabolism. Chem Biol Interact. 2023 Jan 5;369:110278. doi: 10.1016/j.cbi.2022.110278. Epub 2022 Nov 22.
24 Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
25 Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway. Cardiovasc Res. 2000 Feb;45(3):788-94. doi: 10.1016/s0008-6363(99)00369-7.
26 The platelet P2Y12 receptor contributes to granule secretion through Ephrin A4 receptor. Platelets. 2012;23(8):617-25. doi: 10.3109/09537104.2011.645924. Epub 2012 Jan 24.
27 Hormone-sensitive lipase in human adipose tissue, isolated adipocytes, and cultured adipocytes. Pediatr Res. 1982 Dec;16(12):982-8. doi: 10.1203/00006450-198212000-00002.
28 Epidermal growth factor facilitates epinephrine inhibition of P2X7-receptor-mediated pore formation and apoptosis: a novel signaling network. Endocrinology. 2005 Jan;146(1):164-74. doi: 10.1210/en.2004-1026. Epub 2004 Sep 30.
29 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.
30 Evaluation of cytogenetic and DNA damage in human lymphocytes treated with adrenaline in vitro. Toxicol In Vitro. 2015 Feb;29(1):27-33. doi: 10.1016/j.tiv.2014.08.001. Epub 2014 Aug 27.
31 Enzymatic characterization and interspecies difference of phenol sulfotransferases, ST1A forms. Drug Metab Dispos. 2001 Mar;29(3):274-81.
32 Increased arterial pressure in mice with overexpression of the ADHD candidate gene calcyon in forebrain. PLoS One. 2019 Feb 12;14(2):e0211903. doi: 10.1371/journal.pone.0211903. eCollection 2019.