General Information of Drug Combination (ID: DCF2SLS)

Drug Combination Name
IT-141 Epinephrine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs IT-141   DMAYD7O Epinephrine   DM3KJBC
N.A. Small molecular drug
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 1.71
Bliss Independence Score: 1.71
Loewe Additivity Score: 3.89
LHighest Single Agent (HSA) Score: 3.93

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of IT-141
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
IT-141 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Inhibitor [2]
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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 [5]
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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 [6]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [7]
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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 [8]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Metabolism [9]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [10]
Catechol O-methyltransferase (COMT) DEV3T4A COMT_HUMAN Metabolism [11]
Monoamine oxidase type A (MAO-A) DERE4TU AOFA_HUMAN Metabolism [12]
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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 [13]
Solute carrier family 22 member 3 (SLC22A3) OTQYGVXX S22A3_HUMAN Increases Uptake [14]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Increases Expression [15]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [15]
Carbonic anhydrase 2 (CA2) OTJRMUAG CAH2_HUMAN Increases Expression [16]
Integrin alpha-V (ITGAV) OTAM7JTR ITAV_HUMAN Increases Expression [16]
Cathepsin K (CTSK) OTT3YX5O CATK_HUMAN Increases Expression [16]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [17]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [18]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Activity [19]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Cleavage [20]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [20]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Increases Expression [20]
Pyruvate kinase PKM (PKM) OTLHHMC2 KPYM_HUMAN Increases Expression [20]
Alpha-1D adrenergic receptor (ADRA1D) OTW2CD1O ADA1D_HUMAN Increases Activity [21]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [22]
Alpha-1A adrenergic receptor (ADRA1A) OTUIWCL5 ADA1A_HUMAN Increases Activity [21]
Alpha-1B adrenergic receptor (ADRA1B) OTSAYAFD ADA1B_HUMAN Increases Activity [21]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [22]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [22]
Hexokinase-2 (HK2) OTC0GCQO HXK2_HUMAN Increases Expression [20]
Ephrin type-A receptor 4 (EPHA4) OT3AMK0C EPHA4_HUMAN Increases Phosphorylation [23]
Hormone-sensitive lipase (LIPE) OTMMVJ8A LIPS_HUMAN Increases Activity [24]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [20]
P2X purinoceptor 7 (P2RX7) OTNJ9XPL P2RX7_HUMAN Decreases Activity [25]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Increases ADR [26]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Response To Substance [27]
Sulfotransferase 1A3 (SULT1A4) OTHJ8WWV ST1A3_HUMAN Increases Sulfation [28]
Glutathione reductase, mitochondrial (GSR) OTM2TUYM GSHR_HUMAN Increases ADR [26]
Neuron-specific vesicular protein calcyon (CALY) OTQ7EMPU CALY_HUMAN Decreases Secretion [29]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases ADR [26]
Equilibrative nucleoside transporter 4 (SLC29A4) OTWTZXMX S29A4_HUMAN Increases Uptake [14]
Alpha-2A adrenergic receptor (ADRA2A) OTZFGOTP ADA2A_HUMAN Increases ADR [26]
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⏷ Show the Full List of 33 DOT(s)

References

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2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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 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.
6 Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
7 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8 Steroid glucuronides: human circulatory levels and formation by LNCaP cells. J Steroid Biochem Mol Biol. 1991;40(4-6):593-8.
9 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.
10 Adrenal catecholamines and their metabolism in the vitamin A deficient rat. Ann Nutr Metab. 1983;27(3):220-7.
11 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.
12 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.
13 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.
14 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.
15 Epinephrine upregulates superoxide dismutase in human coronary artery endothelial cells. Free Radic Biol Med. 2001 Jan 15;30(2):148-53.
16 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.
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 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.
19 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.
20 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.
21 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.
22 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.
23 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.
24 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.
25 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.
26 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.
27 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.
28 Enzymatic characterization and interspecies difference of phenol sulfotransferases, ST1A forms. Drug Metab Dispos. 2001 Mar;29(3):274-81.
29 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.