General Information of Drug Combination (ID: DCOTFQX)

Drug Combination Name
Nizatidine Quinine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Nizatidine   DMGFV3Z Quinine   DMSWYF5
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: 42.43
Bliss Independence Score: 42.43
Loewe Additivity Score: 52.49
LHighest Single Agent (HSA) Score: 52.51

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Nizatidine
Disease Entry ICD 11 Status REF
Acid-reflux disorder DA22 Approved [2]
Gastric ulcer DA60 Approved [3]
Peptic esophagitis N.A. Approved [3]
Peptic ulcer DA61 Approved [3]
Nizatidine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Histamine H2 receptor (H2R) TTQHJ1K HRH2_HUMAN Antagonist [5]
------------------------------------------------------------------------------------
Nizatidine Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [7]
------------------------------------------------------------------------------------
Nizatidine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Calcitonin (CALCA) OTZ11LHB CALC_HUMAN Increases Expression [8]
Protachykinin-1 (TAC1) OTM842YW TKN1_HUMAN Increases Expression [8]
------------------------------------------------------------------------------------
Indication(s) of Quinine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [4]
Quinine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
E3 ubiquitin-protein ligase COP1 (RFWD2) TT05DLS COP1_HUMAN Modulator [9]
------------------------------------------------------------------------------------
Quinine Interacts with 6 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [11]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [12]
Organic cation/carnitine transporter 2 (SLC22A5) DT3HUVD S22A5_HUMAN Substrate [13]
Organic cation/carnitine transporter 1 (SLC22A4) DT2EG60 S22A4_HUMAN Substrate [14]
Na(+)/Cl(-) betaine/GABA transporter (SLC6A12) DTBPTJF S6A12_HUMAN Substrate [15]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DTP(s)
Quinine Interacts with 8 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [16]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [17]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [18]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [19]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [19]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [20]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [21]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [22]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 DME(s)
Quinine Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Activity [23]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [23]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [23]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Expression [24]
Solute carrier family 22 member 2 (SLC22A2) OTGFK1AL S22A2_HUMAN Decreases Activity [25]
Solute carrier family 22 member 1 (SLC22A1) OT7817I4 S22A1_HUMAN Decreases Activity [25]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Uptake [26]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Activity [27]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Decreases Activity [27]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [24]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [28]
Sodium/hydrogen exchanger 7 (SLC9A7) OTVDLTYA SL9A7_HUMAN Decreases Activity [29]
Solute carrier organic anion transporter family member 1A2 (SLCO1A2) OTO70C5O SO1A2_HUMAN Increases Uptake [30]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 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: 7248).
3 Nizatidine 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: 2510).
5 Does the use of nizatidine, as a pro-kinetic agent, improve gastric emptying in patients post-oesophagectomy J Gastrointest Surg. 2009 Mar;13(3):432-7.
6 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00585)
7 Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
8 Effects of histamine H(2)-receptor antagonists on human plasma levels of calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. J Pharm Pharmacol. 2002 Nov;54(11):1559-63. doi: 10.1211/002235702117.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
10 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
11 Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81.
12 Comparison of type I and type II organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
13 Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84.
14 Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73.
15 The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.22.3.1)
16 Quinine induced simvastatin toxicity through cytochrome inhibition - a case report. BMC Geriatr. 2016 Oct 1;16(1):168.
17 The roles of cytochrome P450 3A4 and 1A2 in the 3-hydroxylation of quinine in vivo. Clin Pharmacol Ther. 1999 Nov;66(5):454-60.
18 Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
19 Drug Interactions Flockhart Table
20 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
21 Identification of human cytochrome P450 isoforms involved in the 3-hydroxylation of quinine by human live microsomes and nine recombinant human cytochromes P450. J Pharmacol Exp Ther. 1996 Dec;279(3):1327-34.
22 Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
23 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
24 Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol. 2002 Nov;58(8):537-42.
25 Involvement of aryl hydrocarbon receptor in the cytotoxicity of corannulene and its derivatives. Toxicol Lett. 2020 Mar 15;321:114-121. doi: 10.1016/j.toxlet.2019.12.012. Epub 2019 Dec 9.
26 Stereoselective transport of hydrophilic quaternary drugs by human MDR1 and rat Mdr1b P-glycoproteins. Br J Pharmacol. 2002 Apr;135(7):1685-94. doi: 10.1038/sj.bjp.0704620.
27 Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
28 Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain. Mol Pharmacol. 2003 May;63(5):1051-8. doi: 10.1124/mol.63.5.1051.
29 Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network. J Biol Chem. 2001 May 18;276(20):17387-94. doi: 10.1074/jbc.M101319200. Epub 2001 Feb 26.
30 Expression of Organic Anion Transporting Polypeptide 1A2 in Red Blood Cells and Its Potential Impact on Antimalarial Therapy. Drug Metab Dispos. 2016 Oct;44(10):1562-8. doi: 10.1124/dmd.116.069807. Epub 2016 Aug 8.