PHLORETIN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H14O5
Molecular Weight	274.2687
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC=C(CCC(=O)C2=C(O)C=C(O)C=C2O)C=C1

InChI

InChIKey=VGEREEWJJVICBM-UHFFFAOYSA-N

InChI=1S/C15H14O5/c16-10-4-1-9(2-5-10)3-6-12(18)15-13(19)7-11(17)8-14(15)20/h1-2,4-5,7-8,16-17,19-20H,3,6H2

HIDE SMILES / InChI

Description
Sources: http://www.hmdb.ca/metabolites/HMDB0003306 | https://www.ncbi.nlm.nih.gov/pubmed/12010860 | https://www.skinceuticals.com/phloretin-cf-635494328004.html

Phloretin is the aglucone of phlorizin, a plant-derived dihydrochalcone phytochemical reported to promote potent antioxidative activities in peroxynitrite scavenging and the inhibition of lipid peroxidation. Phloretin, which is present in apples, pears, and tomatoes, has been found to inhibit the growth of several cancer cells and induce apoptosis of B16 melanoma and HL60 human leukemia cells. Phloretin also inhibits HT-29 cell growth by inducing apoptosis, which may be mediated through changes in mitochondrial membrane permeability and activation of the caspase pathways. Phloretin is a biomarker for the consumption of apples. As for topical application to the skin, phloretin neutralizes damaging free radicals, helps improve cell turnover, and improves the appearance of discoloration.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium/glucose cotransporter 1 7 Target ID: CHEMBL4979 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18063724	Inhibitor 8504		142.0 µM [Ki]
Sodium/glucose cotransporter 2 25 Target ID: CHEMBL3884 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18063724	Inhibitor 8504		25.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Skin environmental exposure 1 Sources: https://www.skinceuticals.com/phloretin-cf-635494328004.html	Palliative		Not Provided 511	PHLORETIN CF Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1025.1 ng/L EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED
3075.9 ng/L EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED
5712.3 ng/L EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
329.5 mg × min/L EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED
1044.6 mg × min/L EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED
2041.1 mg × min/L EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
120.7 min EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED
187.5 min EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED
268.3 min EXPERIMENT https://akjournals.com/view/journals/1326/29/4/article-p443.xml	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	PHLORETIN plasma	Canis lupus familiaris population: HEALTHY age: ADULT sex: MALE food status: FASTED

PubMed

Title	Date	PubMed
The SLC14 gene family of urea transporters.	2004-02	12856182
Glucose transporter in bovine mammary epithelial cells is an asymmetric carrier that exhibits cooperativity and trans-stimulation.	2003-11	12867359
Effective gating charge of ion channels induced by toxin syringomycin E in lipid bilayers.	2003-08	12893306
Functional characterisation of glucose transport in bovine articular chondrocytes.	2003-08	12750890
Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects.	2003-08	12700163
Kinetic evidence that the Na-PO4 cotransporter is the molecular mechanism for Na/Li exchange in human red blood cells.	2003-08	12672655
Characterization of urea transport in Bufo arenarum oocytes.	2003-07-01	12840834
Alternative splicing of NHE-1 mediates Na-Li countertransport and associates with activity rate.	2003-06	12765964
Binding of phlorizin to the isolated C-terminal extramembranous loop of the Na+/glucose cotransporter assessed by intrinsic tryptophan fluorescence.	2003-05-27	12755613
Visualization of specific interaction between biomimetic glycopolymer containing reducing glucose moiety and HepG2 cell mediated by GLUT-1.	2003-05-01	12734805
BK channel openers inhibit migration of human glioma cells.	2003-05	12739163
Influence of molecular dipoles on human skin permeability: Use of 6-ketocholestanol to enhance the transdermal delivery of bacitracin.	2003-05	12712421
Synergistic effects of cystic fibrosis transmembrane conductance regulator and aquaporin-9 in the rat epididymis.	2003-05	12606488
Molecular and functional characterization of a urea transporter from the kidney of the Atlantic stingray.	2003-05	12388386
Influence of phloretin and 6-ketocholestanol on the skin permeation of sodium-fluorescein.	2003-04-29	12711454
Influence of lipophilic counter-ions in combination with phloretin and 6-ketocholestanol on the skin permeation of 5-aminolevulinic acid.	2003-04-14	12672607
Dietary exposure to xenoestrogens in New Zealand.	2003-04	12729260
Glucose uptake and metabolism in the Trichinella spiralis nurse cell.	2003-04	12705933
Inositol transport in preimplantation rabbit embryos: effects of embryo stage, sodium, osmolality and metabolic inhibitors.	2003-04	12683919
Effect of adrenaline on glucose transport in red cells of Rana balcanica.	2003-03	12870702
Non-nutritive bioactive food constituents of plants: bioavailability of flavonoids.	2003-03	12747217
Transformation of flavonoids by intestinal microorganisms.	2003-03	12747214
Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport.	2003-03	12604704
Molecular characterization and partial cDNA cloning of facilitative glucose transporters expressed in human articular chondrocytes; stimulation of 2-deoxyglucose uptake by IGF-I and elevated MMP-2 secretion by glucose deprivation.	2003-02	12554125
Effect of flavonoids on MRP1-mediated transport in Panc-1 cells.	2003-02	12532374
Inhibition of human intestinal brush border membrane vesicle Na+-dependent phosphate uptake by phosphophloretin derivatives.	2003-01-31	12535632
Prolonged activation of Ca2+-activated K+ current contributes to the long-lasting refractory period of Aplysia bag cell neurons.	2002-12-01	12451114
Evidence for vesicles that mediate long-chain fatty acid uptake by human microvascular endothelial cells.	2002-12	12454271
Transport of ketone bodies and lactate in the sheep ruminal epithelium by monocarboxylate transporter 1.	2002-11	12381528
The active and passive components of glucose absorption in rat jejunum under low and high perfusion stress.	2002-10-15	12381828
Transepithelial glucose transport and metabolism in BeWo choriocarcinoma cells.	2002-10-04	12361684
Rapid insertion of GLUT2 into the rat jejunal brush-border membrane promoted by glucagon-like peptide 2.	2002-10-01	12095416
Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT/CD36.	2002-10	12351456
A phosphorylated phloretin derivative. Synthesis and effect on intestinal Na(+)-dependent phosphate absorption.	2002-10	12223344
Analysis of double knockout mice lacking aquaporin-1 and urea transporter UT-B. Evidence for UT-B-facilitated water transport in erythrocytes.	2002-09-27	12133842
Characteristics of L-lactic acid transport in basal membrane vesicles of human placental syncytiotrophoblast.	2002-09	12176739
Urea transporters are distributed in endothelial cells and mediate inhibition of L-arginine transport.	2002-09	12167610
Interactions of ATP, oestradiol, genistein and the anti-oestrogens, faslodex (ICI 182780) and tamoxifen, with the human erythrocyte glucose transporter, GLUT1.	2002-08-01	12133004
Accumulation of intracellular ascorbate from dehydroascorbic acid by astrocytes is decreased after oxidative stress and restored by propofol.	2002-08	12112364
The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids.	2002-07-05	12083758
Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids.	2002-07	12224631
Studies of renal injury IV: The GLUT1 gene protects renal cells from cyclosporine A toxicity.	2002-07	12081571
Transport physiology of the urinary bladder in teleosts: a suitable model for renal urea handling?	2002-06-01	12115926
Flavonoids in human urine as biomarkers for intake of fruits and vegetables.	2002-05	12010860
Role of facilitative glucose uptake in the glucose-inorganic phosphate-mediated retardation and inhibition of development in different strains of mouse embryos.	2002-05	12006097
Regulation of urea permeability in frog urinary bladder by prostaglandin E(2).	2002-05	11976928
The Fluorosome technique for investigating membrane on- and off-loading of drugs by beta-CD and sonicated SUV.	2002-04-10	11959114
Effect of modulators of protein kinase C activity on Ca2+ transport in retinal rod microsomes.	2002-04	11996657
A novel ABC transporter gene, PMR5, is involved in multidrug resistance in the phytopathogenic fungus Penicillium digitatum.	2002-04	11976961
Functional and molecular characterisation of lactic acid transport in bovine articular chondrocytes.	2002	12297728

Patents

Sample Use Guides

In Vivo Use Guide

In the morning after cleansing and toning, apply 4-5 drops of PHLORETIN CF to a dry face, neck, and chest before other skincare products.

Route of Administration: Topical

In Vitro Use Guide

Human esophageal cancer EC-109 cells were incubated with 60, 70, 80, 90 and 100 ug/ml phloretin for 6, 12, 24 and 48 h. It was found that phloretin significantly decreased viable cell numbers in a dose- and time-dependent manner and induced apoptosis in EC-109 cells. Additionally, phloretin exhibited potent anticancer activity in vitro, as evidenced by the downregulation of the anti-apoptosis-associated molecule B-cell lymphoma 2 and an increase in the levels of the apoptosis-associated molecules bcl-2-like protein 4 and tumor protein p53. Phloretin treatment also affected the expression of apoptotic protease activating factor-1, the protein product of the direct binding of the inhibitor of apoptosis protein with low PI to the X-linked inhibitor of apoptosis protein.

Name

Type

Language

PHLORETIN

Official Name

English

FEMA NO. 4390

Preferred Name

English

PHLORETIN [MI]

Common Name

English

3-(4-HYDROXYPHENYL)-1-(2,4,6-TRIHYDROXYPHENYL)-PROPAN-1-ONE [FHFI]

Common Name

English

2',4',6'-TRIHYDROXY-3-(4-HYDROXYPHENYL)PROPIOPHENONE

Systematic Name

English

NSC-407292

Code

English

Code System Code Type Description

CHEBI

17276