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Corynoxine

Alias: Corynoxine; 6877-32-3; CHEBI:70072; methyl (E)-2-[(3S,6'S,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate; 1443767-78-9; Methyl (E)-2-((3S,6'S,7'S,8a'S)-6'-ethyl-2-oxo-2',3',6',7',8',8a'-hexahydro-5'H-spiro[indoline-3,1'-indolizin]-7'-yl)-3-methoxyacrylate; CHEMBL1909424; DTXSID201318329;
Cat No.:V29624 Purity: =99.13%
Corynoxine is a tetracyclic oxindole alkaloid extracted from Uncaria rhynchophylla.
Corynoxine
Corynoxine Chemical Structure CAS No.: 6877-32-3
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of Corynoxine:

  • Corynoxine B
Official Supplier of:
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: =99.13%

Product Description
Corynoxine is a tetracyclic oxindole alkaloid extracted from Uncaria rhynchophylla. Corynoxine is a natural autophagy enhancer that promotes α-synuclein clearance through the Akt/mTOR pathway.
Biological Activity I Assay Protocols (From Reference)
Targets
Natural product; Akt/mTOR
ln Vitro
Corynoxine (6.25-25 μM; 6-12 hours) increases the expression of the autophagy-specific marker LC3-II in N2a and SH-SY5Y cells in a dose-dependent manner [1]. Corynoxine (25 μM; 48 h) increases the breakdown of wild-type (WT) and mutant (A53T) α-syn in inducible PC12 cells through autophagy induction [1].
ln Vivo
The oral gavage of corynoxine (100-100 mg/kg) prolongs the thiopental-induced hypnosis in mice [2]. In Drosophila, corynoxine (10–100 μM, 12 hours) causes autophagy [1].
Enzyme Assay
After treatment, N2a-GFP-LC3 stable cells were fixed with 4 % paraformaldehyde in PBS for 10 min at room temperature. Cells were mounted with FluoSave reagent and imaged with a confocal microscope [1].
Cell Assay
Western Blot Analysis[1]
Cell Types: N2a and SH-SY5Y Cell
Tested Concentrations: 6.25, 12.5, 25 μM
Incubation Duration: 6, 12 hrs (hours)
Experimental Results: Induction of autophagy in neuronal cell lines.
Animal Protocol
Cg-GAL4 fly lines and UAS-GFP-Atg8a fly lines were raised at 25 °C on standard corn meal medium supplemented with dry yeast. Drugs were initially dissolved in DMSO then diluted in water to desired concentrations. The drug- containing water was added to instant Drosophila food and mixed thoroughly. As the control, the same amount of DMSO was also mixed with instant Drosophila food. For the treatment, Cg-GAL4 fly lines were crossed to UAS-GFP-Atg8a fly lines at 25 °C, and then transferred the 2nd instar larvae of Cg-GAL4 > UAS-GFP-Atg8a onto instant food containing different concentrations of Cory (10–100 μM), 100 μM Cory B (positive control) or 0.1 % DMSO (negative control) for 12 h at 25 °C. Treated larvae were collected and fat bodies were dissected out in PBS, and then fixed with 4 % paraformaldehyde for 10 min at room temperature. Tissues were mounted with FluorSave™ Reagent (Merck) and imaged with a confocal microscopy [1].
References

[1]. Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway. J Neuroimmune Pharmacol. 2014 Jun;9(3):380-7.

[2]. Effect of oxindole alkaloids from the hooks of Uncaria macrophylla on thiopental-induced hypnosis. Phytomedicine. 1998 Apr;5(2):83-6.

Additional Infomation
Corynoxine is a member of indolizines. It has a role as a metabolite.
Corynoxine has been reported in Uncaria macrophylla, Mitragyna speciosa, and Uncaria attenuata with data available.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C22H28N2O4
Molecular Weight
384.4687
Exact Mass
384.204
CAS #
6877-32-3
Related CAS #
Corynoxine B;17391-18-3;Corynoxine hydrochloride
PubChem CID
10475115
Appearance
White to off-white solid powder
Density
1.2±0.1 g/cm3
Boiling Point
560.8±50.0 °C at 760 mmHg
Melting Point
166-168ºC
Flash Point
293.0±30.1 °C
Vapour Pressure
0.0±1.5 mmHg at 25°C
Index of Refraction
1.596
Source
Uncaria rhynchophylla
LogP
3.31
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
5
Rotatable Bond Count
5
Heavy Atom Count
28
Complexity
663
Defined Atom Stereocenter Count
4
SMILES
O=C1[C@]2(C3=C([H])C([H])=C([H])C([H])=C3N1[H])C([H])([H])C([H])([H])N1C([H])([H])[C@@]([H])(C([H])([H])C([H])([H])[H])[C@@]([H])(/C(=C(/[H])\OC([H])([H])[H])/C(=O)OC([H])([H])[H])C([H])([H])[C@]12[H]
InChi Key
DAXYUDFNWXHGBE-NRAMRBJXSA-N
InChi Code
InChI=1S/C22H28N2O4/c1-4-14-12-24-10-9-22(17-7-5-6-8-18(17)23-21(22)26)19(24)11-15(14)16(13-27-2)20(25)28-3/h5-8,13-15,19H,4,9-12H2,1-3H3,(H,23,26)/b16-13+/t14-,15+,19+,22+/m1/s1
Chemical Name
methyl (E)-2-[(3S,6'S,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate
Synonyms
Corynoxine; 6877-32-3; CHEBI:70072; methyl (E)-2-[(3S,6'S,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate; 1443767-78-9; Methyl (E)-2-((3S,6'S,7'S,8a'S)-6'-ethyl-2-oxo-2',3',6',7',8',8a'-hexahydro-5'H-spiro[indoline-3,1'-indolizin]-7'-yl)-3-methoxyacrylate; CHEMBL1909424; DTXSID201318329;
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 (~260.10 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.50 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 (6.50 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.

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Solubility in Formulation 3: 30 mg/mL (78.03 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.6010 mL 13.0049 mL 26.0098 mL
5 mM 0.5202 mL 2.6010 mL 5.2020 mL
10 mM 0.2601 mL 1.3005 mL 2.6010 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)
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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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