General Information of Drug Combination (ID: DC4QG5J)

Drug Combination Name
Pinacidil Tetracycline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Pinacidil   DMRADYL Tetracycline   DMZA017
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: 49.23
Bliss Independence Score: 49.23
Loewe Additivity Score: 63.26
LHighest Single Agent (HSA) Score: 63.27

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Pinacidil
Disease Entry ICD 11 Status REF
High blood pressure BA00 Approved [2]
Pinacidil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Potassium channel unspecific (KC) TT1VOHK NOUNIPROTAC Modulator [5]
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Pinacidil Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
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Indication(s) of Tetracycline
Disease Entry ICD 11 Status REF
Acne vulgaris ED80 Approved [3]
Actinomycosis N.A. Approved [3]
Acute gonococcal cervicitis N.A. Approved [3]
Acute gonococcal epididymo-orchitis N.A. Approved [3]
Bacterial infection 1A00-1C4Z Approved [4]
Bronchitis CA20 Approved [3]
Brucellosis N.A. Approved [3]
Lymphogranuloma venereum N.A. Approved [3]
Ornithosis N.A. Approved [3]
Pneumonia CA40 Approved [3]
Q fever N.A. Approved [3]
Relapsing fever N.A. Approved [3]
Rickettsialpox N.A. Approved [3]
Rocky mountain spotted fever N.A. Approved [3]
Syphilis N.A. Approved [3]
Trachoma N.A. Approved [3]
Typhus N.A. Approved [3]
Urinary tract infection GC08 Approved [3]
Yaws N.A. Approved [3]
Pelvic inflammatory disease GA05 Investigative [3]
Sinusitis CA0A.Z Investigative [3]
Tetracycline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2) TTQ8KVI F4NA87_STAAU Binder [8]
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Tetracycline Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [11]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [11]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Substrate [11]
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Tetracycline Interacts with 44 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Increases Transport [12]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Increases Uptake [11]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Activity [13]
Glutathione S-transferase Mu 3 (GSTM3) OTLA2WJT GSTM3_HUMAN Decreases Activity [13]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [7]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [7]
Asparagine synthetase (ASNS) OT8R922G ASNS_HUMAN Increases Expression [7]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [7]
AP-1 complex subunit sigma-1A (AP1S1) OTQ2H8DN AP1S1_HUMAN Decreases Expression [7]
Transgelin (TAGLN) OTAEZ0KP TAGL_HUMAN Decreases Expression [7]
Fibronectin type III domain-containing protein 4 (FNDC4) OTOQK0WK FNDC4_HUMAN Increases Expression [7]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [7]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [14]
Alternative prion protein (PRNP) OTE85L1Q APRIO_HUMAN Affects Binding [15]
Claudin-11 (CLDN11) OTNN6UTL CLD11_HUMAN Decreases Expression [16]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [17]
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Decreases Activity [17]
Integrin alpha-5 (ITGA5) OT3RCI67 ITA5_HUMAN Increases Expression [16]
Insulin-like growth factor-binding protein 1 (IGFBP1) OT6UQV2K IBP1_HUMAN Increases Expression [18]
Integrin alpha-M (ITGAM) OTAG6HWU ITAM_HUMAN Decreases Expression [16]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [19]
Integrin alpha-L (ITGAL) OTCUQAIS ITAL_HUMAN Decreases Expression [16]
Neutrophil collagenase (MMP8) OTZXH19L MMP8_HUMAN Decreases Activity [17]
Integrin alpha-3 (ITGA3) OTBCH21D ITA3_HUMAN Decreases Expression [16]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [20]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [20]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Increases Expression [18]
Collagenase 3 (MMP13) OTY8BZIE MMP13_HUMAN Decreases Activity [17]
Gap junction alpha-8 protein (GJA8) OTZCPRKD CXA8_HUMAN Decreases Expression [16]
Microsomal triglyceride transfer protein large subunit (MTTP) OTNUVSDT MTP_HUMAN Decreases Expression [18]
Claudin-15 (CLDN15) OT9K0KI7 CLD15_HUMAN Decreases Expression [16]
Claudin-6 (CLDN6) OTEN8ID2 CLD6_HUMAN Decreases Expression [16]
Claudin-8 (CLDN8) OT7IIWXG CLD8_HUMAN Decreases Expression [16]
Claudin-2 (CLDN2) OTRF3D6Y CLD2_HUMAN Decreases Expression [16]
Claudin-10 (CLDN10) OT2CVAKY CLD10_HUMAN Decreases Expression [16]
Peroxisomal bifunctional enzyme (EHHADH) OTBAAHL5 ECHP_HUMAN Decreases Expression [18]
Diacylglycerol O-acyltransferase 2 (DGAT2) OTE5PDD0 DGAT2_HUMAN Increases Expression [20]
Neurogenic locus notch homolog protein 4 (NOTCH4) OTBCHB61 NOTC4_HUMAN Decreases Expression [16]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Increases Expression [21]
Gap junction delta-2 protein (GJD2) OTDR288R CXD2_HUMAN Decreases Expression [16]
Neurogenic locus notch homolog protein 3 (NOTCH3) OTMVVA7F NOTC3_HUMAN Decreases Expression [16]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Increases Export [11]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Increases Transport [22]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Increases Export [11]
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⏷ Show the Full List of 44 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: 2412).
3 Tetracycline FDA Label
4 How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6 Cytochrome P450 3A4-mediated oxidative conversion of a cyano to an amide group in the metabolism of pinacidil. Biochemistry. 2002 Feb 26;41(8):2712-8.
7 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
8 The glycylcyclines: a comparative review with the tetracyclines. Drugs. 2004;64(1):63-88.
9 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.
10 Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
11 Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76.
12 Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
13 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.
14 A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97.
15 Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in vitro. J Mol Biol. 2000 Jul 28;300(5):1309-22. doi: 10.1006/jmbi.2000.3840.
16 Effects of residual levels of tetracycline on the barrier functions of human intestinal epithelial cells. Food Chem Toxicol. 2017 Nov;109(Pt 1):253-263. doi: 10.1016/j.fct.2017.09.004. Epub 2017 Sep 4.
17 Synthesis and in vitro evaluation of targeted tetracycline derivatives: effects on inhibition of matrix metalloproteinases. Bioorg Med Chem. 2007 Mar 15;15(6):2368-74. doi: 10.1016/j.bmc.2007.01.026. Epub 2007 Jan 19.
18 Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis. Toxicol Appl Pharmacol. 2016 Jul 1;302:1-9. doi: 10.1016/j.taap.2016.04.007. Epub 2016 Apr 16.
19 Old drug, new target: ellipticines selectively inhibit RNA polymerase I transcription. J Biol Chem. 2013 Feb 15;288(7):4567-82. doi: 10.1074/jbc.M112.411611. Epub 2013 Jan 4.
20 Increased hepatic Fatty Acid uptake and esterification contribute to tetracycline-induced steatosis in mice. Toxicol Sci. 2015 Jun;145(2):273-82. doi: 10.1093/toxsci/kfv049. Epub 2015 Mar 4.
21 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
22 Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96.