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: CHEMBL245067
  CAS Number: CAS 60-81-1
  TTD Drug ID: DMNARGO
  VARIDT Drug ID: DR00950

Molecule-Related Drug Atlas

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	[5]
LIK-066	DM32NWD	Heart failure	BD10-BD13	Phase 2	[6]
YG1699	DM1NR1J	Type-1 diabetes	5A10	Phase 2	[7]
1614235 + 2330672	DMD751X	Type-2 diabetes	5A11	Phase 1	[6]
GSK1614235	DM7I1AQ	Type-2 diabetes	5A11	Phase 1	[8]
LX2761	DM8ZS7T	Type 2 diabetes	5A11	Phase 1	[9]
T-1095	DMGFS51	Diabetic complication	5A2Y	Discontinued in Phase 2	[10]
KURAIDIN	DMLDUJ1	Discovery agent	N.A.	Investigative	[11]
KURARINONE	DMH0G8W	Discovery agent	N.A.	Investigative	[11]
10-methoxy-N(1)-methylburnamine-17-O-veratrate	DMJW25X	Discovery agent	N.A.	Investigative	[12]

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	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[15]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[16]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[22]

Molecular Interaction Atlas of This Drug

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
UDP-glucuronosyltransferase 1A1	OTH1C8OJ	UD11_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 1A10	OTOTZVEY	UD110_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 1A3	OTUEOER3	UD13_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 1A7	OTY4JJ32	UD17_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 1A8	OTTMABBG	UD18_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 1A9	OTPCHAFX	UD19_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 2B15	OTABTFU2	UDB15_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 2B17	OTSVIF4E	UDB17_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 2B4	OTSZZP0B	UD2B4_HUMAN	Gene/Protein Processing	[4]
UDP-glucuronosyltransferase 2B7	OT2Q71VQ	UD2B7_HUMAN	Gene/Protein Processing	[4]

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] 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.
• [5] 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.
• [6] 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).
• [7] 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.
• [8] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [9] Clinical pipeline report, company report or official report of Lexicon Pharmaceuticals.
• [10] T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999 Sep;48(9):1794-800.
• [11] Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007 May 15;15(10):3445-9.
• [12] 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.
• [13] 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.
• [14] Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011 Nov;39(11):2155-61.
• [15] Mammalian multidrug-resistance proteins (MRPs). Essays Biochem. 2011 Sep 7;50(1):179-207.
• [16] 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.
• [17] Multidrug resistance associated protein 2 mediates transport of prostaglandin E2. Liver Int. 2006 Apr;26(3):362-8.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.