 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C21H28O12 |
| Molecular Weight | 472.44 |
| Exact Mass | 472.158 |
| CAS # | 7061-54-3 |
| Related CAS # | Phlorizin;60-81-1 |
| PubChem CID | 9912668 |
| Appearance | White to off-white solid powder |
| Boiling Point | 770ºC at 760 mmHg |
| Melting Point | 113-114 °C(lit.) |
| Flash Point | 270.7ºC |
| LogP | 1.2 |
| Hydrogen Bond Donor Count | 9 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 33 |
| Complexity | 581 |
| Defined Atom Stereocenter Count | 5 |
| SMILES | O1[C@]([H])([C@@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C([H])([H])O[H])O[H])O[H])O[H])OC1=C([H])C(=C([H])C(=C1C(C([H])([H])C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H])=O)O[H])O[H] |
| InChi Key | IOUVKUPGCMBWBT-QNDFHXLGSA-N |
| InChi Code | 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 |
| 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 |
| Synonyms | Phlorizin dihydrate; 7061-54-3; Phloridzin dihydrate; MFCD00149438; Phlorizin, dihydrate; Phlorizin (dihydrate); 1-Propanone,1-[2-(b-D-glucopyranosyloxy)-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)-,dihydrate; Phloridzin dihydrate [MI]; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
- Sodium-glucose cotransporter 1 (SGLT1) (Ki = 0.2 μM in rabbit intestinal brush-border membranes) [4] - Sodium-glucose cotransporter 2 (SGLT2) (IC50 = 3.9 μM in rat renal cortex) [3] |
| ln Vitro |
- Inhibition of intestinal glucose absorption: Phloridzin (0.1-10 μM) inhibited Na+-dependent glucose uptake in rabbit intestinal brush-border membrane vesicles, with maximum inhibition (~80%) at 10 μM. This effect was competitive with glucose, as indicated by increased Km values for glucose uptake without changing Vmax [4] - Inhibition of renal glucose reabsorption: In rat renal cortex slices, Phloridzin (1-50 μM) reduced Na+-dependent glucose uptake in a concentration-dependent manner, with 50% inhibition at 3.9 μM. It had no significant effect on Na+-independent glucose transport [3] |
| ln Vivo |
- Antihyperglycemic effect in diabetic rats: In streptozotocin-induced diabetic rats, intravenous administration of Phloridzin (5-20 mg/kg) dose-dependently reduced blood glucose levels by 30-60% within 1 hour, accompanied by a 5-10-fold increase in urinary glucose excretion. The effect lasted for 2-4 hours [2] - Glucose tolerance improvement: In normal rats, oral Phloridzin (50 mg/kg) administered 30 minutes before an oral glucose load (2 g/kg) reduced the postprandial glucose peak by ~40% and blunted the glucose excursion over 2 hours [2] - Effect on insulin and glucagon: In diabetic rats, Phloridzin (10 mg/kg, i.v.) increased plasma insulin levels by ~25% and decreased glucagon levels by ~20% at 1 hour post-administration, possibly due to improved glucose utilization [1] |
| Enzyme Assay |
- SGLT activity in brush-border membranes: Rabbit intestinal brush-border membrane vesicles were prepared and incubated with Phloridzin (0.1-100 μM) in the presence of [¹⁴C]-glucose and Na+ gradient. After 10 minutes, vesicles were filtered, and radioactivity was measured. Kinetic parameters (Km, Vmax) were calculated to determine competitive inhibition [4] - Renal SGLT inhibition assay: Rat renal cortex slices were incubated with Phloridzin (1-50 μM) and [¹⁴C]-glucose in Na+-containing or Na+-free buffer. Glucose uptake was measured after 30 minutes, and IC50 was determined from the dose-response curve [3] |
| Cell Assay |
Renal cell glucose uptake assay: Primary cultures of rat renal proximal tubule cells were treated with Phloridzin (5-50 μM) and [³H]-glucose in medium with or without Na+. After 1 hour, cells were lysed, and radioactivity was counted to assess Na+-dependent glucose uptake [3] |
| Animal Protocol |
- Diabetic rat model: Streptozotocin-induced diabetic rats (blood glucose >300 mg/dL) were anesthetized, and Phloridzin (5, 10, 20 mg/kg) was administered via tail vein injection. Blood glucose was measured at 0, 30, 60, 120, and 240 minutes using a glucometer. Urine was collected over 4 hours to quantify glucose excretion via colorimetric assay [2] - Oral glucose tolerance test: Normal rats were fasted overnight, then given Phloridzin (50 mg/kg) by oral gavage. Thirty minutes later, they received an oral glucose load (2 g/kg). Blood glucose was measured at 0, 30, 60, 90, and 120 minutes [2] |
| ADME/Pharmacokinetics |
- Oral absorption: Phloridzin has low oral bioavailability (~10%) in rats due to hydrolysis by intestinal β-glucosidases, producing phloretin and glucose [2] - Metabolism: In vivo, Phloridzin is rapidly metabolized to phloretin (aglycone) in the intestine and liver, which is further conjugated with glucuronic acid [2] - Excretion: In rats, intravenously administered Phloridzin (10 mg/kg) is excreted primarily in urine (60-70%) within 24 hours, mostly as metabolites [2] |
| Toxicity/Toxicokinetics |
- Acute toxicity: In mice, the LD50 of Phloridzin after intraperitoneal injection is ~500 mg/kg, with death occurring within 24 hours due to severe hypoglycemia [2] - Chronic toxicity: Rats treated with Phloridzin (20 mg/kg/day, i.p.) for 4 weeks showed no significant changes in liver or kidney function tests, but slight weight loss (~5%) was observed [1] |
| References |
[1]. Endokrynol Pol. 2010 May-Jun;61(3):303-10. [2]. Diabetes Metab Res Rev. 2005 Jan-Feb;21(1):31-8. [3]. J Pharmacol Exp Ther. 2008 Mar;324(3):985-91. [4]. J Biochem. 1977 May;81(5):1511-5. |
| Additional Infomation |
- Phloridzin is a natural glycoside isolated from apple tree bark (Malus pumila). It was one of the first identified SGLT inhibitors and serves as a prototype for the development of SGLT2 inhibitors used in type 2 diabetes treatment [1][2] - Its mechanism of action involves blocking renal glucose reabsorption and intestinal glucose absorption, thereby reducing blood glucose levels through increased urinary glucose excretion [3][4] |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1167 mL | 10.5834 mL | 21.1667 mL | |
| 5 mM | 0.4233 mL | 2.1167 mL | 4.2333 mL | |
| 10 mM | 0.2117 mL | 1.0583 mL | 2.1167 mL |