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Phloretic acid

Alias: NSC-40949; NSC 40949; Phloretic acid
Cat No.:V18642 Purity: ≥98%
Desaminotyrosine is a microbiome-associated metabolite that blocks the development of influenza by amplifying type I interferon signaling.
Phloretic acid
Phloretic acid Chemical Structure CAS No.: 501-97-3
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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500mg
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Product Description
Desaminotyrosine is a microbiome-associated metabolite that blocks the development of influenza by amplifying type I interferon signaling.
Phloretic acid, also known as desaminotyrosine or 3-(4-hydroxyphenyl)propionic acid, is a microbiome-associated metabolite and a plant-derived phenolic compound. It is a hydroxy monocarboxylic acid composed of a propionic acid molecule with a 4-hydroxyphenyl group at the 3-position. This natural product is found in various sources including tea plants and the resin of Boswellia carterii. Phloretic acid has gained attention for its role in augmenting type I interferon signaling, which provides protection against influenza virus infection. It is also known as NSC-40949 and has a molecular formula of C9H10O3 and a molecular weight of 166.18.
Biological Activity I Assay Protocols (From Reference)
Targets
Phloretic acid acts through the augmentation of type I interferon (IFN) signaling. It is a microbiome-associated metabolite that influences the host immune response to viral infection. By amplifying type I IFN responses, it blocks the development of influenza. This mechanism suggests its primary biological target is the type I interferon signaling pathway, although it does not directly bind to a specific receptor like a traditional drug. It is also a plant metabolite that is functionally related to propionic acid.
ln Vitro
Phloretic acid exhibits antiviral activity by amplifying type I interferon signaling. As a phenolic compound, it also possesses antioxidant properties that may aid in exploring oxidative stress mitigation during viral infection. It has been reported to be present in tea plants and other organisms with relevant biological data. Its activity is associated with its role as a microbially associated metabolite that influences host defense mechanisms.
ln Vivo
Deaminated tyrosine is produced in nanomolar levels per gram of excrement by wild-type mice, and picomoles of this substance are found in serum. The mice's survival or weight loss was unaffected by treatment with deaminotyrosine (200 mM) prior to influenza infection, which protects against influenza through type I interferon (IFN) signaling with or without vancomycin, neomycin, ampicillin, and metronidazole (VNAM). Through mouse type I IFN amplification, deaminated tyrosine increases type I IFN in macrophages [1].
In vivo studies have demonstrated that phloretic acid provides protection against influenza infection. Mice treated with phloretic acid (200 mM) prior to influenza infection showed improved survival, an effect mediated through type I interferon signaling. This protection was observed with or without the presence of antibiotics such as vancomycin, neomycin, ampicillin, and metronidazole, indicating the compound's direct action on the host immune system rather than through modulation of the microbiome. The metabolite is produced in nanomolar levels per gram of excrement in wild-type mice and is found in picomolar concentrations in serum.
Enzyme Assay
Phloretic acid is evaluated in cell-free assays to assess its antioxidant properties and its role as a metabolite. Its purity and identity can be confirmed using techniques such as HPLC and NMR analysis. The compound's ability to interact with components of the interferon signaling pathway can be studied using biochemical assays that measure the activation of interferon-stimulated genes or the phosphorylation of key signaling molecules like STAT1. However, specific detailed protocols for cell-free enzymatic assays are not well-documented.
Cell Assay
Phloretic acid is assessed in cell-based assays to evaluate its antiviral and immune-modulating effects. Macrophages treated with phloretic acid show increased type I interferon production. This leads to an enhanced antiviral state, protecting cells from influenza virus infection. The compound's effects on interferon signaling can be quantified by measuring the expression of interferon-stimulated genes using qPCR or by assessing the phosphorylation of STAT proteins via Western blot. Its antioxidant activity can also be evaluated in cell culture models of oxidative stress.
Animal Protocol
Phloretic acid is administered orally in animal models to study its protective effects against influenza. In these studies, mice are treated with the compound prior to infection, and survival rates and weight loss are monitored as key endpoints. The compound's ability to amplify type I interferon signaling is confirmed by measuring interferon levels in the serum or tissues of treated mice. The use of knockout mice for interferon receptors can further validate the mechanism of action.
ADME/Pharmacokinetics
Metabolism / Metabolites
4-Hydroxy-4-hydroxyphenylpropionic acid is a known human metabolite of 3,4-dihydroxyphenylpropionic acid.
Phloretic acid is a known human metabolite of 3,4-dihydroxyphenylpropionic acid. It has a molecular formula of C9H10O3, a molecular weight of 166.18, and a CAS number of 501-97-3. Its logP is 1.1, and it has a density of 1.3±0.1 g/cm³. The compound is an off-white to yellow solid powder with a melting point of 129-131 °C. It is soluble in DMSO at 90 mg/mL and is typically stored as a powder at -20°C for up to 3 years.
Toxicity/Toxicokinetics
No detailed toxicity data is available for phloretic acid. It is a naturally occurring metabolite and is generally considered safe for research purposes. The compound is for research use only and is not intended for human therapeutic use. In animal studies, treatment with phloretic acid did not affect the mice's survival or weight loss, suggesting a favorable safety profile at the doses used.
References

[1]. The microbial metabolite desaminotyrosine protects from influenza through type I interferon. Science. 2017 Aug 4;357(6350):498-502.

Additional Infomation
Phlorenic acid is a hydroxy monocarboxylic acid composed of a propionic acid molecule with a 4-hydroxyphenyl group linked at the 3-position. It is a plant metabolite functionally related to propionic acid and is the conjugate acid of phlorenic acid esters. It has been reported that 3-(4-hydroxyphenyl)propionic acid is present in tea plants (Camellia sinensis), spring flowers (Spiranthes vernalis), and several other organisms with relevant data.
Phloretic acid is also known as desaminotyrosine, NSC-40949, and 3-(4-hydroxyphenyl)propionic acid. It is a plant metabolite and an endogenous metabolite. Its role in augmenting type I interferon signaling highlights its potential as a natural product for studying antiviral immunity and host-microbiome interactions. It is not approved for clinical use and is supplied for research purposes only.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C9H10O3
Molecular Weight
166.18
Exact Mass
166.062
CAS #
501-97-3
PubChem CID
10394
Appearance
Off-white to yellow solid powder
Density
1.3±0.1 g/cm3
Boiling Point
352.4±17.0 °C at 760 mmHg
Melting Point
129-131 °C(lit.)
Flash Point
181.1±17.4 °C
Vapour Pressure
0.0±0.8 mmHg at 25°C
Index of Refraction
1.580
LogP
1.1
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
3
Heavy Atom Count
12
Complexity
148
Defined Atom Stereocenter Count
0
InChi Key
NMHMNPHRMNGLLB-UHFFFAOYSA-N
InChi Code
InChI=1S/C9H10O3/c10-8-4-1-7(2-5-8)3-6-9(11)12/h1-2,4-5,10H,3,6H2,(H,11,12)
Chemical Name
3-(4-hydroxyphenyl)propanoic acid
Synonyms
NSC-40949; NSC 40949; Phloretic acid
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)
Solubility Data
Solubility (In Vitro)
DMSO : ~100 mg/mL (~601.76 mM)
H2O : ~33.33 mg/mL (~200.57 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (15.04 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (15.04 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (15.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


Solubility in Formulation 4: 100 mg/mL (601.76 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 6.0176 mL 30.0879 mL 60.1757 mL
5 mM 1.2035 mL 6.0176 mL 12.0351 mL
10 mM 0.6018 mL 3.0088 mL 6.0176 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

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