Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMNARGO)

Drug Name
Phlorizin Drug Info
Synonyms
Phlorizin; Phloridzin; 60-81-1; Phlorhizin; Phlorizoside; Floridzin; Phlorrhizin; Phloretin 2'-glucoside; Phlorrhizen; Phloridzosid; Phlorizine; UNII-CU9S17279X; Phloretin-2'-O-beta-glucoside; AI3-19835; NSC 2833; Phloridzin dihydrate; EINECS 200-487-1; Phloretin-2'-beta-glucoside; CHEBI:8113; CHEMBL245067; IOUVKUPGCMBWBT-QNDFHXLGSA-N; CU9S17279X; 2'-(beta-D-Glucopyranosyloxy)-4',6'-dihydroxy-3-(4-hydroxyphenyl)propiophenone; 1-[2-(beta-D-Glucopyranosyloxy)-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)-1-propanone; 1-Propanone, 1-(2-(b
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Cross-matching ID
PubChem CID
6072
ChEBI ID
CHEBI:8113
CAS Number
CAS 60-81-1
TTD Drug ID
DMNARGO
VARIDT Drug ID
DR00950

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DTP
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Discontinued Drug(s)
Investigative Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Sodium/glucose cotransporter 1 (SGLT1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sotagliflozin DMMLXA9 Heart failure BD10-BD13 Approved [8]
LIK-066 DM32NWD Heart failure BD10-BD13 Phase 2 [9]
YG1699 DM1NR1J Type-1 diabetes 5A10 Phase 2 [10]
1614235 + 2330672 DMD751X Type-2 diabetes 5A11 Phase 1 [9]
GSK1614235 DM7I1AQ Type-2 diabetes 5A11 Phase 1 [11]
LX2761 DM8ZS7T Type 2 diabetes 5A11 Phase 1 [12]
T-1095 DMGFS51 Diabetic complication 5A2Y Discontinued in Phase 2 [13]
KURAIDIN DMLDUJ1 Discovery agent N.A. Investigative [14]
KURARINONE DMH0G8W Discovery agent N.A. Investigative [14]
10-methoxy-N(1)-methylburnamine-17-O-veratrate DMJW25X Discovery agent N.A. Investigative [15]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Multidrug resistance-associated protein 2 (ABCC2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [16]
Methotrexate DM2TEOL Anterior urethra cancer Approved [17]
Folic Acid DMEMBJC Colorectal carcinoma Approved [18]
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [19]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [20]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [21]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [22]
Sulfasalazine DMICA9H Irritable bowel syndrome DD91.0 Approved [23]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [24]
Oxaliplatin DMQNWRD Adenocarcinoma 2D40 Approved [25]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Nitric oxide synthase 3 (NOS3)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [26]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [27]
Bosentan DMIOGBU Pulmonary arterial hypertension BB01.0 Approved [28]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [29]
Methotrexate DM2TEOL Anterior urethra cancer Approved [30]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [31]
Quercetin DM3NC4M Obesity 5B81 Approved [32]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [33]
Fructose DM43AN2 Vomiting MD90 Approved [34]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [35]
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Drug(s) Affected By Sodium/glucose cotransporter 2 (SLC5A2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [36]
Dapagliflozin DM28UJG Non-insulin dependent diabetes 5A11 Approved [6]
PF-04971729 DM79VXT Type-2 diabetes 5A11 Approved [37]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [38]
Canagliflozin DMFRM1I Non-insulin dependent diabetes 5A11 Approved [6]
Bexagliflozin DMK56G0 Type 2 diabetes 5A11 Approved [39]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [40]
Urethane DM7NSI0 N. A. N. A. Phase 4 [41]
Remogliflozin etabonate DMW4YK1 Type-1/2 diabetes 5A10-5A11 Phase 2 [6]
Benzo(a)pyrene DMN7J43 N. A. N. A. Phase 1 [42]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Sodium/glucose cotransporter 1 (SLC5A1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [36]
Hydroquinone DM6AVR4 Melasma ED60.1 Approved [43]
Ethanol DMDRQZU Chronic pain MG30 Approved [44]
Amphotericin B DMTAJQE Acne vulgaris ED80 Approved [45]
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [46]
Triclosan DMZUR4N Malaria 1F40-1F45 Approved [47]
3,4-Dihydroxycinnamic Acid DMVZL26 Thrombocytopenia 3B64 Phase 4 [48]
Resveratrol DM3RWXL Giant cell arteritis 4A44.2 Phase 3 [49]
CERC-801 DM3SZ7P N. A. N. A. Phase 2 [50]
Benzo(a)pyrene DMN7J43 N. A. N. A. Phase 1 [42]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Sodium/glucose cotransporter 1 (SGLT1) TT2UE56 SC5A1_HUMAN Inhibitor [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Gene/Protein Processing [4]
Sodium/glucose cotransporter 1 (SLC5A1) OT0T78JI SC5A1_HUMAN Drug Response [5]
Sodium/glucose cotransporter 2 (SLC5A2) OT93UUDI SC5A2_HUMAN Gene/Protein Processing [6]
UDP-glucuronosyltransferase 1A1 OTH1C8OJ UD11_HUMAN Gene/Protein Processing [7]
UDP-glucuronosyltransferase 1A10 OTOTZVEY UD110_HUMAN Gene/Protein Processing [7]
UDP-glucuronosyltransferase 1A3 OTUEOER3 UD13_HUMAN Gene/Protein Processing [7]
UDP-glucuronosyltransferase 1A7 OTY4JJ32 UD17_HUMAN Gene/Protein Processing [7]
UDP-glucuronosyltransferase 1A8 OTTMABBG UD18_HUMAN Gene/Protein Processing [7]
UDP-glucuronosyltransferase 1A9 OTPCHAFX UD19_HUMAN Gene/Protein Processing [7]
UDP-glucuronosyltransferase 2B15 OTABTFU2 UDB15_HUMAN Gene/Protein Processing [7]

References

1 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: 4757).
2 J Biol Chem. 1988 Jan 5;263(1):187-92.High affinity phlorizin binding to the LLC-PK1 cells exhibits a sodium:phlorizin stoichiometry of 2:1.
3 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.
4 Physiological concentrations of dietary polyphenols regulate vascular endothelial cell expression of genes important in cardiovascular health. Br J Nutr. 2010 May;103(10):1398-403.
5 D-Glucose-recognition and phlorizin-binding sites in human sodium/D-glucose cotransporter 1 (hSGLT1): a tryptophan scanning study. Biochemistry. 2007 Nov 27;46(47):13616-28. doi: 10.1021/bi701193x. Epub 2007 Nov 6.
6 Discovery of novel N--D-xylosylindole derivatives as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycemia in diabetes. J Med Chem. 2011 Jan 13;54(1):166-78. doi: 10.1021/jm101072y. Epub 2010 Dec 3.
7 Phloretin exhibits potential food-drug interactions by inhibiting human UDP-glucuronosyltransferases in vitro. Toxicol In Vitro. 2022 Oct;84:105447. doi: 10.1016/j.tiv.2022.105447. Epub 2022 Jul 19.
8 LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012 Aug;92(2):158-69.
9 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. (Target id: 915).
10 ClinicalTrials.gov (NCT04956263) A Comparison of Postprandial Glucose After a Mixed Meal Tolerance Test, and the Metabolic Effects of Insulin Withdrawal in a Crossover Study of the Dual Systemic SGLT1 and SGLT2 Inhibitor YG1699, and the Selective SGLT2 Inhibitor Dapagliflozin in Subjects With Type 1 Diabetes. U.S.National Institutes of Health.
11 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
12 Clinical pipeline report, company report or official report of Lexicon Pharmaceuticals.
13 T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999 Sep;48(9):1794-800.
14 Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007 May 15;15(10):3445-9.
15 Alstiphyllanines E-H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter. Bioorg Med Chem. 2010 Mar 15;18(6):2152-2158.
16 Involvement of the drug transporters p glycoprotein and multidrug resistance-associated protein Mrp2 in telithromycin transport. Antimicrob Agents Chemother. 2006 Jan;50(1):80-7.
17 Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011 Nov;39(11):2155-61.
18 Mammalian multidrug-resistance proteins (MRPs). Essays Biochem. 2011 Sep 7;50(1):179-207.
19 Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2. Oncol Lett. 2016 Sep;12(3):2107-2114.
20 Multidrug resistance associated protein 2 mediates transport of prostaglandin E2. Liver Int. 2006 Apr;26(3):362-8.
21 Lentivirus-mediated RNAi silencing targeting ABCC2 increasing the sensitivity of a human nasopharyngeal carcinoma cell line against cisplatin. J Transl Med. 2008 Oct 4;6:55.
22 Effect of acetaminophen on expression and activity of rat liver multidrug resistance-associated protein 2 and P-glycoprotein. Biochem Pharmacol. 2004 Aug 15;68(4):791-8.
23 Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7.
24 Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos. 2002 Apr;30(4):457-63.
25 Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
26 Protective effects of S-carvedilol on doxorubicin-induced damages to human umbilical vein endothelial cells and rats. J Appl Toxicol. 2019 Aug;39(8):1233-1244. doi: 10.1002/jat.3809. Epub 2019 May 7.
27 Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. J Cardiovasc Pharmacol. 2002 Oct;40(4):625-31.
28 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.
29 Hydrogen peroxide decreases endothelial nitric oxide synthase promoter activity through the inhibition of Sp1 activity. DNA Cell Biol. 2009 Mar;28(3):119-29.
30 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
31 Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs. Am J Respir Crit Care Med. 2005 Oct 15;172(8):987-93. doi: 10.1164/rccm.200501-041OC. Epub 2005 Jul 7.
32 A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide. 2005 Mar;12(2):97-104.
33 The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells. J Diabetes Complications. 2006 Sep-Oct;20(5):336-42.
34 Fructose induces the inflammatory molecule ICAM-1 in endothelial cells. J Am Soc Nephrol. 2008 Sep;19(9):1712-20.
35 Upregulation of nitric oxide production in vascular endothelial cells by all-trans retinoic acid through the phosphoinositide 3-kinase/Akt pathway. Circulation. 2005 Aug 2;112(5):727-36. doi: 10.1161/CIRCULATIONAHA.104.500959. Epub 2005 Jul 25.
36 Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5.
37 Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors. J Med Chem. 2011 Apr 28;54(8):2952-60. doi: 10.1021/jm200049r. Epub 2011 Mar 30.
38 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
39 EGT1442, a potent and selective SGLT2 inhibitor, attenuates blood glucose and HbA(1c) levels in db/db mice and prolongs the survival of stroke-prone rats. Pharmacol Res. 2011 Apr;63(4):284-93. doi: 10.1016/j.phrs.2011.01.001. Epub 2011 Jan 5.
40 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
41 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
42 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
43 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
44 Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
45 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
46 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
47 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
48 Glucose absorption regulation and mechanism of the compounds in Lilium lancifolium Thunb on Caco-2?cells. Food Chem Toxicol. 2021 Mar;149:112010. doi: 10.1016/j.fct.2021.112010. Epub 2021 Jan 22.
49 Absorption of resveratrol by vascular endothelial cells through passive diffusion and an SGLT1-mediated pathway. J Nutr Biochem. 2013 Nov;24(11):1823-9. doi: 10.1016/j.jnutbio.2013.04.003. Epub 2013 Aug 6.
50 Sodium-independent low-affinity D-glucose transport by human sodium/D-glucose cotransporter 1: critical role of tryptophan 561. Biochemistry. 2007 Mar 13;46(10):2758-66. doi: 10.1021/bi061696x. Epub 2007 Feb 9.