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Peretinoin

Cat No.:V12871 Purity: ≥98%
Peretinoin is an oral acyclic retinoid with a retinoid structure that targets retinoid nuclear receptors like RXR and RAR.
Peretinoin
Peretinoin Chemical Structure CAS No.: 81485-25-8
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
Peretinoin is an oral acyclic retinoid with a retinoid structure that targets retinoid nuclear receptors like RXR and RAR. Peretinoin reduces SPHK1 mRNA levels in vitro by downregulating the transcription factor Sp1. Peretinoin activates the autophagy pathway by increasing Atg16L1 expression and prevents the development of non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Peretinoin inhibits HCV (hepatitis C virus) RNA amplification and virus release by changing lipid metabolism, with EC50 of 9 μM.
Biological Activity I Assay Protocols (From Reference)
ln Vitro
Even at 10 μM, peretinoin (10–40 μM; 12-72 hours) demonstrated suppressed SPHK1 expression after 24 hours of treatment; this effect became more pronounced after 72 hours [1]. promotes autophagy corrosion and upregulates the expression of LC3B-II in mouse primary hepatocytes [2]. Assay for Cell Autophagy[2]
Cell Assay
Cell Autophagy Assay[2]
Cell Types: Mouse primary hepatocytes (MPH) and human HCC HepG2 cell line
Tested Concentrations: 5 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: Upregulates the expression of LC3B-II and increases autophagy flux.

Western Blot Analysis[1]
Cell Types: Human liver cancer (Huh-7) Cell
Tested Concentrations: 10, 20 and 40 μM
Incubation Duration: 12, 24, 48 and 72 hrs (hours)
Experimental Results: After 24 hrs (hours) of treatment, SPHK1 expression was inhibited, even after 10 microns.
References

[1]. Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma. BMC Cancer. 2013 Apr 15;13:191.

[2]. Peretinoin, an acyclic retinoid, suppresses steatohepatitis and tumorigenesis by activating autophagy in mice fed an atherogenic high-fat diet. Oncotarget. 2017 Jun 20;8(25):39978-39993.

[3]. Peretinoin, an acyclic retinoid, inhibits hepatocarcinogenesis by suppressing sphingosine kinase 1 expression in vitro and in vivo. Sci Rep. 2017 Dec 5;7(1):16978.

Additional Infomation
Peretinoin is an orally available, acyclic retinoid with potential antineoplastic and chemopreventive activities. Peretinoin binds to and activates nuclear retinoic acid receptors (RAR), which in turn recruit coactivator proteins and promote, with other transcriptional complexes, the transcription of target genes. As a result, this agent may modulate the expression of genes involved in the regulation of cell proliferation, cell differentiation, and apoptosis of both normal and tumor cells.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C20H30O2
Molecular Weight
302.451006412506
Exact Mass
302.225
CAS #
81485-25-8
PubChem CID
6437836
Appearance
Light yellow to yellow solid powder
LogP
5.992
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
2
Rotatable Bond Count
9
Heavy Atom Count
22
Complexity
496
Defined Atom Stereocenter Count
0
SMILES
CC(=CCC/C(=C/CC/C(=C/C=C/C(=C/C(=O)O)/C)/C)/C)C
InChi Key
UUBHZHZSIKRVIV-KCXSXWJSSA-N
InChi Code
InChI=1S/C20H30O2/c1-16(2)9-6-10-17(3)11-7-12-18(4)13-8-14-19(5)15-20(21)22/h8-9,11,13-15H,6-7,10,12H2,1-5H3,(H,21,22)/b14-8+,17-11+,18-13+,19-15+
Chemical Name
(2E,4E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,4,6,10,14-pentaenoic 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

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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 : ~50 mg/mL (~165.32 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 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 (8.27 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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 (8.27 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.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.3063 mL 16.5317 mL 33.0633 mL
5 mM 0.6613 mL 3.3063 mL 6.6127 mL
10 mM 0.3306 mL 1.6532 mL 3.3063 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.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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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.

Biological Data
  • Peretinoin pharmacokinetics study design and change of gene expression profiling. A: Peretinoin pharmacokinetics study design. Twelve patients were enrolled in the study and two groups of 6 patients were randomly administered one of two doses of peretinoin (600 or 300 mg per day) for 8 weeks. A liver biopsy was obtained before the start of peretinoin administration and 8 weeks into the treatment. After the second liver biopsy, oral administration of peretinoin twice daily was resumed for 88 weeks. B: Hierarchical clustering analysis of patients using all expressed genes. Patient numbers (Table 1) and peretinoin dose are listed. Patients with HCC recurrence are shown in red and boxed. There was no significant association between hepatic gene expression and HCC recurrence before starting peretinoin treatment, while distinct clusters of patients were observed after week 8 depending on HCC recurrence.[1].Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma. BMC Cancer. 2013 Apr 15;13:191.
  • Expression profiling of 224 gene predictors and the prognosis of patients. A: Hierarchical clustering using 224 gene predictors of patients with or without HCC recurrence. Patients with HCC recurrence within 2 years are shown in red and patients with HCC recurrence after the cessation of peretinoin are boxed in red. B: Pathway analysis of differentially expressed genes using MetaCore (GeneGo). Functional ontology enrichment analysis was performed to find differentially expressed pathway maps or map folders using 224 differentially expressed genes (p<0.002) between patients with and without HCC recurrence. C, D: Kaplan-Meier estimation of recurrence-free ratio (C) and survival ratio (D) of patients with recurrence expression patterns (red) and those with non-recurrence expression (blue).[1].Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma. BMC Cancer. 2013 Apr 15;13:191.
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