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| Targets |
Corynoxeine is a potent inhibitor of ERK1/ERK2 phosphorylation induced by PDGF-BB. It suppresses PDGF-BB-induced vascular smooth muscle cell (VSMC) proliferation by blocking extracellular signal-regulated kinase 1/2 phosphorylation. The compound has no 5-HT2A activity, eliminating serotonergic confounding. It inhibits PDGF receptor β (PDGF-Rβ) phosphorylation, activation of Akt, phospholipase C (PLC) γ1, and mitogen-activated protein kinase (MAPK/ERK)-activated kinase 1 and 2 (MEK1/2).
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| ln Vitro |
Corynoxeine works by suppressing PDGF-BB-induced ERK1/2 activation, which in turn prevents VSMC proliferation when activated by PDGF-BB. Corynoxeine preincubation of VSMC significantly inhibited PDGF-BB-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Corynoxeine also inhibited phosphorylation of PDGF receptor β (PDGF-Rβ), activation of Akt or phospholipase C (PLC) γ 1 activation, and mitogen-activated protein kinase (MAPK/ERK)-activated kinase 1 and 2 (MEK1/2). Corynoxeine reduces DNA synthesis and VSMC proliferation within the same dose range that it inhibits PDGF-BB-induced ERK1/2 activation. When exposed to PDGF-BB, corynoxeine reduces the number of VSMCs by 50% (IC50) at a concentration of 13.7 μM. With an IC50 of 9.2 μM, corynoxeine suppresses DNA synthesis in response to PDGF-BB (24 hours). When VSMCs were pretreated with Corynoxeine (5-50 μM) for a full day, the number of cells was significantly reduced without causing any cytotoxicity; the percentages of inhibition at 5, 20, and 50 μM were 25.0±12.5, 63.0±27.5, and 88.0±, respectively. 12.5%. Additionally, without causing any cytotoxicity, corynoxeine considerably reduced the amount of VSMC DNA synthesis that was triggered by 50 ng/mL PDGF-BB in a concentration-dependent manner. The inhibition rates were 32.8±11.0 and 51.8±8.0 at 5, 20, and 50 μM, respectively. and 76.9±7.4% [1].
Corynoxeine inhibits VSMC proliferation in response to PDGF-BB with an IC50 of 13.7 μM for cell count and 9.2 μM for DNA synthesis. It reduces DNA synthesis and VSMC proliferation within the same dose range that it inhibits ERK1/2 activation. Preincubation of VSMCs with Corynoxeine (5-50 μM) significantly reduced cell numbers without causing cytotoxicity, with inhibition percentages of 25.0±12.5% at 5 μM, 63.0±27.5% at 20 μM, and 88.0±12.5% at 50 μM. It also concentration-dependently inhibited PDGF-BB-induced DNA synthesis. |
| ln Vivo |
Corynoxeine shows in vivo nephroprotection at 5-20 mg/kg/day via Nrf2/HO-1 and NF-κB pathways. It has been detected in the brain following in vivo administration. The compound is commonly used as a reference compound for investigating stereochemistry-dependent bioactivity, alkaloid pharmacology, and quality control of Uncaria-derived herbal materials. In vivo formulation can be prepared as a homogeneous suspension for oral administration.
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| Enzyme Assay |
In vitro enzyme assays for Corynoxeine involve measuring ERK1/2 kinase activity inhibition. Kinase activity is assessed using suitable substrates and ATP, with product formation monitored by phosphorylation-specific antibodies or radioactive detection. IC50 values of 13.7 μM (cell count) and 9.2 μM (DNA synthesis) are determined from dose-response curves in VSMC proliferation assays. PDGF-Rβ phosphorylation, Akt activation, and MEK1/2 activation are assessed by Western blot. For receptor selectivity, 5-HT2A receptor binding assays are performed to confirm no off-target activity.
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| Cell Assay |
In vitro cell-based assays for Corynoxeine are conducted in vascular smooth muscle cells (VSMCs). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with the compound at varying concentrations (5-50 μM). VSMC proliferation is induced by PDGF-BB (50 ng/mL). Cell proliferation is assessed by cell counting and DNA synthesis is measured by [3H]-thymidine incorporation. ERK1/2 phosphorylation is analyzed by Western blot. Cell viability is assessed by standard assays such as MTT to confirm lack of cytotoxicity.
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| Animal Protocol |
In vivo animal studies for Corynoxeine are conducted in rodent models. The compound is administered orally at doses of 5-20 mg/kg/day. For nephroprotection studies, Nrf2/HO-1 and NF-κB pathway activation is assessed in kidney tissues. For vascular studies, VSMC proliferation and restenosis models are used. Blood samples are collected for pharmacokinetic analysis. The compound can be formulated as a homogeneous suspension for oral administration. Animals are monitored for clinical signs, and tissues are collected for histopathological and biomarker analysis at study endpoints.
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| ADME/Pharmacokinetics |
Corynoxeine (MW 382.45 g/mol, C22H26N2O4) has a density of 1.3±0.1 g/cm³, a boiling point of 562.7±50.0 °C at 760 mmHg, and a melting point of 210 °C. It is soluble in DMSO at 76 mg/mL (198.71 mM) and ethanol at 7 mg/mL (18.3 mM), but insoluble in water. For in vivo administration, it can be formulated as a homogeneous suspension. The compound is stable as a powder at -20°C for 3 years and at 4°C for 2 years; in solvent at -80°C for 6 months and at -20°C for 1 month.
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| Toxicity/Toxicokinetics |
Corynoxeine is generally well-tolerated in preclinical studies. It shows no cytotoxicity in VSMCs at concentrations up to 50 μM. The compound has been studied for neuroprotective, antihypertensive, anti-inflammatory, and sedative-related activities with acceptable safety profiles. No significant adverse effects have been reported in the available literature at research-use concentrations. The compound is intended for research use only. Standard safety precautions should be followed when handling. Comprehensive toxicological evaluation would be required for therapeutic development.
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| References | |
| Additional Infomation |
Corynoxeine is an indole compound. It has been reported in Uncaria rhynchophylla, Hymenochloa crus-galli, and other organisms with relevant data. See also: Cat's Claw (partial).
Corynoxeine is an oxindole alkaloid primarily isolated from Uncaria rhynchophylla (Gouteng). It is a potent ERK1/ERK2 inhibitor of PDGF-BB-induced VSMC proliferation with an IC50 of 13.7 μM. The compound has no 5-HT2A activity, making it useful for vascular biology and restenosis research. It is commonly used as a reference compound for investigating stereochemistry-dependent bioactivity and quality control of Uncaria-derived herbal materials. All applications are limited to non-human research use. |
| Molecular Formula |
C22H26N2O4
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| Molecular Weight |
382.4528
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| Exact Mass |
382.189
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| CAS # |
630-94-4
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| PubChem CID |
44568160
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
562.7±50.0 °C at 760 mmHg
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| Melting Point |
210℃
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| Flash Point |
294.1±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.606
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| LogP |
3.07
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
690
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CO/C=C(\[C@H]1C[C@H]2[C@@]3(CCN2C[C@@H]1C=C)C4=CC=CC=C4NC3=O)/C(=O)OC
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| InChi Key |
MUVGVMUWMAGNSY-KAXDATADSA-N
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| InChi Code |
InChI=1S/C22H26N2O4/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/h4-8,13-15,19H,1,9-12H2,2-3H3,(H,23,26)/b16-13+/t14-,15-,19-,22+/m0/s1
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| Chemical Name |
methyl (E)-2-[(3R,6'R,7'S,8'aS)-6'-ethenyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ≥ 3.8 mg/mL (~9.94 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6147 mL | 13.0736 mL | 26.1472 mL | |
| 5 mM | 0.5229 mL | 2.6147 mL | 5.2294 mL | |
| 10 mM | 0.2615 mL | 1.3074 mL | 2.6147 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.
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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