PhlorizinNa+-glucose cotransporter (SGLT) inhibitor CAS# 60-81-1 |
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Cas No. | 60-81-1 | SDF | Download SDF |
PubChem ID | 6072 | Appearance | White-yellowish powder |
Formula | C21H24O10 | M.Wt | 436.4 |
Type of Compound | Chalcones | Storage | Desiccate at -20°C |
Synonyms | Floridzin; NSC 2833 | ||
Solubility | DMSO : ≥ 50 mg/mL (114.57 mM) H2O : 1 mg/mL (2.29 mM; Need ultrasonic) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | 1-[2,4-dihydroxy-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]-3-(4-hydroxyphenyl)propan-1-one | ||
SMILES | C1=CC(=CC=C1CCC(=O)C2=C(C=C(C=C2OC3C(C(C(C(O3)CO)O)O)O)O)O)O | ||
Standard InChIKey | IOUVKUPGCMBWBT-QNDFHXLGSA-N | ||
Standard InChI | InChI=1S/C21H24O10/c22-9-16-18(27)19(28)20(29)21(31-16)30-15-8-12(24)7-14(26)17(15)13(25)6-3-10-1-4-11(23)5-2-10/h1-2,4-5,7-8,16,18-24,26-29H,3,6,9H2/t16-,18-,19+,20-,21-/m1/s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Phlorizin is a non-selective SGLT inhibitor with Kis of 300 and 39 nM for hSGLT1 and hSGLT2, respectively. Phlorizin is also a Na+/K+-ATPase inhibitor. Phlorizin may be a novel therapeutic approach for the treatment of diabetic nephrolog, it protects mice from diabetic nephrology. Phlorizin prevents ventricular tachyarrhythmia through the improvement of impulse conduction slowing during ischemia. |
Targets | TNF-α | hSGLT1 | hSGLT2 | ATPase | Sodium Channel | Calcium Channel |
In vitro | Competitive inhibition of SGLT2 by tofogliflozin or phlorizin induces urinary glucose excretion through extending splay in cynomolgus monkeys.[Pubmed: 24761001]Am J Physiol Renal Physiol. 2014 Jun 15;306(12):F1520-33.Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed a glucose lowering effect in type 2 diabetes patients through inducing renal glucose excretion. Detailed analysis of the mechanism of the glucosuric effect of SGLT2 inhibition, however, has been hampered by limitations of clinical study.
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In vivo | Beneficial effects of phlorizin on diabetic nephropathy in diabetic db/db mice.[Pubmed: 24927646]J Diabetes Complications. 2014 Sep-Oct;28(5):596-603.This study observes the effects of Phlorizin on diabetic nephrology in db/db diabetic mice and explores possible underlying mechanisms.
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Animal Research | Phlorizin prevents electrically-induced ventricular tachyarrhythmia during ischemia in langendorff-perfused guinea-pig hearts.[Pubmed: 24989008 ]Biol Pharm Bull. 2014;37(7):1168-76.Phlorizin is a type of flavonoids and has a peroxynitrite scavenging effect. This study aimed to elucidate the effects of Phlorizin on ischemia-induced ventricular tachyarrhythmia (VT).
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Phlorizin Dilution Calculator
Phlorizin Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.2915 mL | 11.4574 mL | 22.9148 mL | 45.8295 mL | 57.2869 mL |
5 mM | 0.4583 mL | 2.2915 mL | 4.583 mL | 9.1659 mL | 11.4574 mL |
10 mM | 0.2291 mL | 1.1457 mL | 2.2915 mL | 4.583 mL | 5.7287 mL |
50 mM | 0.0458 mL | 0.2291 mL | 0.4583 mL | 0.9166 mL | 1.1457 mL |
100 mM | 0.0229 mL | 0.1146 mL | 0.2291 mL | 0.4583 mL | 0.5729 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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Phlorizin is a non-selective SGLT inhibitor with Kis of 300 and 39 nM for hSGLT1 and hSGLT2, respectively. Phlorizin is also a Na+/K+-ATPase inhibitor.
In Vitro:Phlorizin is a non-selective SGLT inhibitor with Kis of 300 and 39 nM for hSGLT1 and hSGLT2, respectively[1]. Phlorizin is also a Na+/K+-ATPase inhibitor[2]. Phlorizin at 2×10-4 M inhibits Na+ and Rb+-activated ATPase activities in human red cell membranes by 43 %. At 1 mM and 7 mM RbCl, rubidium uptake is not changed or is slightly inhibited (less than 15 %) by 2×10-4 M Phlorizin[2]. Cell viability is not significantly altered by doses of Phlorizin <100 μM. Pretreating cells with Phlorizin does not significantly reduce nitrite or PGE2 levels. Phlorizin does not suppress IL-6 or TNF-α production, although 100 μM Phlorizin can significantly inhibit TNF-α expression[3].
In Vivo:Prior to Phlorizin treatment, the blood glucose level in SDT fatty rats is 370±49 mg/dL. Six hours after dosing, the blood glucose level in the Phlorizin treated group decreases to an almost normal level (139±32 mg/dL). Phlorizin-treated SDT fatty rats are heavier than vehicle-treated SDT fatty rats after 12 weeks. Phlorizin treatment significantly decreases glucose excretion and delays insulin decreases. Creatinine clearance decreases significantly with Phlorizin treatment. 23 weeks of Phlorizin treatment prevents the decrease of nerve fibers (23.6±3.2 fibers/mm). Retinal abnormalities are completely prevented with Phlorizin[4].
References:
[1]. Pajor AM, et al. Inhibitor binding in the human renal low- and high-affinity Na+/glucose cotransporters. J Pharmacol Exp Ther. 2008 Mar;324(3):985-91.
[2]. Nakagawa A, et al. Localization of the phlorizin site on Na, K-ATPase in red cell membranes. J Biochem. 1977 May;81(5):1511-5.
[3]. Chang WT, et al. Evaluation of the anti-inflammatory effects of phloretin and phlorizin in lipopolysaccharide-stimulated mouse macrophages. Food Chem. 2012 Sep 15;134(2):972-9.
[4]. Katsuda Y, et al. Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin. Exp Anim. 2015;64(2):161-9.
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Phlorizin prevents electrically-induced ventricular tachyarrhythmia during ischemia in langendorff-perfused guinea-pig hearts.[Pubmed:24989008]
Biol Pharm Bull. 2014;37(7):1168-76.
Phlorizin is a type of flavonoids and has a peroxynitrite scavenging effect. This study aimed to elucidate the effects of Phlorizin on ischemia-induced ventricular tachyarrhythmia (VT). Optical signals from the epicardial surface of the ventricle or left ventricular end diastolic pressure (LVEDP) were recorded during acute global ischemia in 42 Langendorff-perfused guinea pig hearts. Experiments were performed in the control condition and in the presence of Phlorizin or N-2-mercaptopropionylglycine (2-MPG), a peroxynitrite scavenger, respectively. Mean action potential duration at 20 min of ischemia did not differ among the three interventions. Impulse conduction time-dependently slowed during 20 min of ischemia in the control. Phlorizin but not 2-MPG improved the ischemic conduction slowing at 15 and 20 min of ischemia. Programmed stimulation induced VT at 20 min of ischemia in the control and in the presence of 2-MPG but not in the presence of Phlorizin (p<0.05). LVEDP was increased during 30 min of ischemia in the control and in the presence of 2-MPG but not in the presence of Phlorizin. These results indicate that Phlorizin prevents VT through the improvement of impulse conduction slowing during ischemia. Phlorizin may be more useful for ischemia-induced VT than 2-MPG.
Beneficial effects of phlorizin on diabetic nephropathy in diabetic db/db mice.[Pubmed:24927646]
J Diabetes Complications. 2014 Sep-Oct;28(5):596-603.
AIMS: This study observes the effects of Phlorizin on diabetic nephrology in db/db diabetic mice and explores possible underlying mechanisms. METHODS: Sixteen diabetic db/db mice and eight age-matched db/m mice were divided into three groups: vehicle-treated diabetic group (DM group), diabetic group treated with Phlorizin (DMT group) and normal control group (CC group). Phlorizin was given in normal saline solution by intragastric administration for 10 weeks. Differentially expressed proteins in three groups were identified using iTRAQ quantitative proteomics and the data were further analyzed with ingenuity pathway analysis. RESULTS: The body weight and serum concentrations of fasting blood glucose (FBG), advanced glycation end products (AGEs), total cholesterol, triglycerides, blood urea nitrogen, creatinine and 24-h urine albumin were increased in the DM group compared to those of the CC group (P<0.05), and they were decreased by treatment with Phlorizin (P<0.05). Morphologic observations showed Phlorizin markedly attenuated renal injury. Phlorizin prevented diabetic nephropathy by regulating the expression of a series of proteins involved in renal and urological disease, molecular transport, free radical scavenging, and lipid metabolism. CONCLUSIONS: Phlorizin protects mice from diabetic nephrology and thus may be a novel therapeutic approach for the treatment of diabetic nephrology.
Competitive inhibition of SGLT2 by tofogliflozin or phlorizin induces urinary glucose excretion through extending splay in cynomolgus monkeys.[Pubmed:24761001]
Am J Physiol Renal Physiol. 2014 Jun 15;306(12):F1520-33.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed a glucose lowering effect in type 2 diabetes patients through inducing renal glucose excretion. Detailed analysis of the mechanism of the glucosuric effect of SGLT2 inhibition, however, has been hampered by limitations of clinical study. Here, we investigated the mechanism of urinary glucose excretion using nonhuman primates with SGLT inhibitors tofogliflozin and Phlorizin, both in vitro and in vivo. In cells overexpressing cynomolgus monkey SGLT2 (cSGLT2), both tofogliflozin and Phlorizin competitively inhibited uptake of the substrate (alpha-methyl-d-glucopyranoside; AMG). Tofogliflozin was found to be a selective cSGLT2 inhibitor, inhibiting cSGLT2 more strongly than did Phlorizin, with selectivity toward cSGLT2 1,000 times that toward cSGLT1; Phlorizin was found to be a nonselective cSGLT1/2 inhibitor. In a glucose titration study in cynomolgus monkeys under conditions of controlled plasma drug concentration, both tofogliflozin and Phlorizin increased fractional excretion of glucose (FEG) by up to 50% under hyperglycemic conditions. By fitting the titration curve using a newly introduced method that avoids variability in estimating the threshold of renal glucose excretion, we found that tofogliflozin and Phlorizin lowered the threshold and extended the splay in a dose-dependent manner without significantly affecting the tubular transport maximum for glucose (TmG). Our results demonstrate the contribution of SGLT2 to renal glucose reabsorption (RGR) in cynomolgus monkeys and demonstrate that competitive inhibition of cSGLT2 exerts a glucosuric effect by mainly extending splay and lowering threshold without affecting TmG.
Phlorizin: a review.[Pubmed:15624123]
Diabetes Metab Res Rev. 2005 Jan-Feb;21(1):31-8.
The dihydrochalcone Phlorizin is a natural product and dietary constituent found in a number of fruit trees. It has been used as a pharmaceutical and tool for physiology research for over 150 years. Phlorizin's principal pharmacological action is to produce renal glycosuria and block intestinal glucose absorption through inhibition of the sodium-glucose symporters located in the proximal renal tubule and mucosa of the small intestine. This review covers the role Phlorizin has played in the history of diabetes mellitus and its use as an agent to understand fundamental concepts in renal physiology as well as summarizes the physiology of cellular glucose transport and the pathophysiology of renal glycosuria. It reviews the biology and pathobiology of glucose transporters and discusses the medical botany of Phlorizin and the potential effects of plant flavonoids, such as Phlorizin, on human metabolism. Lastly, it describes the clinical pharmacology and toxicology of Phlorizin, including investigational uses of Phlorizin and Phlorizin analogs in the treatment of diabetes, obesity, and stress hyperglycemia.
Renal Na(+)-glucose cotransporters.[Pubmed:11133510]
Am J Physiol Renal Physiol. 2001 Jan;280(1):F10-8.
In humans, the kidneys filter approximately 180 g of D-glucose from plasma each day, and this is normally reabsorbed in the proximal tubules. Although the mechanism of reabsorption is well understood, Na(+)-glucose cotransport across the brush-border membrane and facilitated diffusion across the basolateral membrane, questions remain about the identity of the genes responsible for cotransport across the brush border. Genetic studies suggest that two different genes regulate Na(+)-glucose cotransport, and there is evidence from animal studies to suggest that the major bulk of sugar is reabsorbed in the convoluted proximal tubule by a low-affinity, high-capacity transporter and that the remainder is absorbed in the straight proximal tubule by a high-affinity, low-capacity transporter. There are at least three different candidates for these human renal Na(+)-glucose cotransporters. This review will focus on the structure-function relationships of these three transporters, SGLT1, SGLT2, and SGLT3.
Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats.[Pubmed:3571496]
J Clin Invest. 1987 May;79(5):1510-5.
Insulin resistance is characteristic of the diabetic state. To define the role of hyperglycemia in generation of the insulin resistance, we examined the effect of Phlorizin treatment on tissue sensitivity to insulin in partially pancreatectomized rats. Five groups were studied: group I, sham-operated controls; group II, partially pancreatectomized diabetic rats with moderate glucose intolerance; group III, diabetic rats treated with Phlorizin to normalize glucose tolerance; group IV, Phlorizin-treated controls; and group V, Phlorizin-treated diabetic rats restudied after discontinuation of Phlorizin. Insulin sensitivity was assessed with the euglyemic hyperinsulinemic clamp technique in awake, unstressed rats. Insulin-mediated glucose metabolism was reduced by approximately 30% (P less than 0.001) in diabetic rats. Phlorizin treatment of diabetic rats completely normalized insulin sensitivity but had no effect on insulin action in controls. Discontinuation of Phlorizin in Phlorizin-treated diabetic rats resulted in the reemergence of insulin resistance. These data demonstrate that a reduction of beta-cell mass leads to the development of insulin resistance, and correction of hyperglycemia with Phlorizin, without change in insulin levels, normalizes insulin sensitivity. These results provide the first in vivo evidence that hyperglycemia per se can lead to the development of insulin resistance.