| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Cbl
Hydrocotarnine primarily targets Cbl (Casitas B-lineage lymphoma proto-oncogene), an E3 ubiquitin ligase that negatively regulates NLRP3 inflammasome activation. By inhibiting Cbl, hydrocotarnine relieves the suppression of NLRP3 inflammasome, leading to increased secretion of IL-1β and IL-18. This mechanism involves the SFK-Cbl axis in regulating NLRP3 inflammasome activation. The compound also increases the expression of GLUT1 and enhances cellular glucose uptake in glycolytic metabolism, indicating its role in metabolic regulation. Hydrocotarnine's analgesic properties are mediated through its effects on pain pathways, making it relevant for cancer pain research. |
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| ln Vitro |
Picrotin has an IC50 value of 13.1 μM and is sensitive to α2 GlyR[1].The analgesic hydrocotarnine (CRIN-2) has patent WO2011160016A2[1]. In THP-1 cells, hydrocotarnine (10 μM; 1 hour) raises the secretion of IL-1β and IL-18, while tyrosine-phosphorylated protein levels overall are increased by (0.1–10 μM; 1 hour) [1]. THP-1-derived macrophages' glycolytic and glycolytic reserve capacities are increased by hydrocotarnine (50 μM; 0-100 min) [2]. In THP-1-derived macrophages, hydrocotarnine (50 μM; 16 hours) inhibits Cbl and raises total GLUT1 protein [2]. It is well recognized that hydrocotanine lessens cancer pain and increases the analgesic effects of opioids [3].
In vitro studies have demonstrated that hydrocotarnine (10 μM; 1 hour) raises the secretion of IL-1β and IL-18 in THP-1 cells, while tyrosine-phosphorylated protein levels are increased at concentrations of 0.1–10 μM. In THP-1-derived macrophages, hydrocotarnine (50 μM; 0-100 min) increases glycolytic and glycolytic reserve capacities. The compound (50 μM; 16 hours) inhibits Cbl and raises total GLUT1 protein levels in these cells. Hydrocotarnine has an IC50 value of 13.1 μM against picrotin-sensitive α2 GlyR. It is well recognized that hydrocotarnine lessens cancer pain and increases the analgesic effects of opioids. Western blot analysis shows that hydrocotarnine induces p-Pyk2 loss and increases tyrosine phosphorylated proteins in a dose-dependent manner. |
| ln Vivo |
Hydrocotarnine (10 mg/kg/d; ip; 9 d) has an inhibitory effect on Cbl and causes an increase in IL-18 levels, indicating enhanced activation of the NLRP3 inflammasome in mice [1]. Hydrocotarnine (10 mg/kg/d; i.p.; 9 d) protects mice from DSS-induced colitis with lower scores on pathological assessments of inflammation, epithelial defects, and crypt atrophy [1].
In vivo, hydrocotarnine (10 mg/kg/day; intraperitoneal; 9 days) has an inhibitory effect on Cbl and causes an increase in IL-18 levels, indicating enhanced activation of the NLRP3 inflammasome in mice. The same dosing regimen protects mice from dextran sulfate sodium (DSS)-induced colitis, with lower scores on pathological assessments of inflammation, epithelial defects, and crypt atrophy. In DSS-induced C57BL/6 mouse colitis models (6-9 weeks old), hydrocotarnine administered at 10 mg/kg intraperitoneally once daily for 9 days dramatically attenuated weight loss compared with PBS-treated control mice. These results suggest that reducing negative regulation of NLRP3 inflammasome activation can alleviate colitis in animal models. |
| Enzyme Assay |
For in vitro enzyme/receptor binding assays, hydrocotarnine can be evaluated using cell-free systems to assess its interactions with Cbl and other molecular targets. Binding studies may employ purified Cbl protein to measure direct compound-protein interactions using techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Enzyme activity assays can be performed to evaluate the compound's inhibitory effects on Cbl E3 ubiquitin ligase activity using appropriate substrates. Receptor binding assays may be conducted to assess hydrocotarnine's affinity for α2 GlyR and other receptors. IC50 and Kd values are determined through dose-response curves. These cell-free assays help elucidate the primary molecular mechanisms underlying hydrocotarnine's anti-inflammatory and analgesic activities.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: THP-1 Cell Tested Concentrations: 0.1, 1, 10 μM Incubation Duration: 1 hour Experimental Results: Induces p-Pyk2 loss and increases the levels of tyrosine phosphorylated proteins in a dose-dependent manner. In vitro cellular assays for hydrocotarnine are commonly performed using THP-1 human monocytic cells and THP-1-derived macrophages. Cells are cultured in standard media and treated with hydrocotarnine at concentrations ranging from 0.1 to 50 μM for various durations (1 hour to 16 hours). Cytokine secretion (IL-1β and IL-18) is measured using ELISA. Tyrosine-phosphorylated protein levels are assessed by Western blotting using anti-phosphotyrosine antibodies. Glycolytic function is evaluated using Seahorse extracellular flux analysis to measure extracellular acidification rates (ECAR). GLUT1 protein expression is analyzed by Western blotting. Western blot analysis for p-Pyk2 is also performed. |
| Animal Protocol |
Animal/Disease Models: DSS-induced C57BL/6 mouse colitis model (6-9 weeks old) [1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day; 9 days, 2.5% DSS treatment from day 1 Start on day 7 and end on day 7 Experimental Results: Weight loss in mice with DSS-induced colitis was Dramatically attenuated compared with PBS-treated control mice, suggesting that reducing negative regulation of NLRP3 inflammasome activation can alleviate colitis in animal models middle. In vivo animal experiments with hydrocotarnine are conducted using the DSS-induced C57BL/6 mouse colitis model. Male or female C57BL/6 mice (6-9 weeks old) are administered 2.5% DSS in drinking water starting on day 1 to induce colitis. Hydrocotarnine is administered intraperitoneally at 10 mg/kg once daily for 9 days, starting on day 7. Body weight is monitored daily as an indicator of disease severity. At study endpoint, colon tissues are harvested for pathological assessment of inflammation, epithelial defects, and crypt atrophy. IL-18 levels are measured in colon tissues or serum to assess NLRP3 inflammasome activation. Comparison with PBS-treated control mice allows evaluation of treatment efficacy. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of hydrocotarnine are not extensively documented in the available literature. As a tetrahydroisoquinoline alkaloid with a molecular weight of approximately 221.25 g/mol (free base), it is expected to have moderate oral bioavailability. The compound's analgesic properties suggest it can reach effective concentrations in the central nervous system. For in vivo studies, hydrocotarnine is typically administered via intraperitoneal injection at 10 mg/kg. The compound's stability and solubility characteristics have not been fully characterized. Detailed PK parameters such as half-life, Cmax, Tmax, AUC, and protein binding are not available, and researchers often refer to general alkaloid pharmacokinetic profiles for experimental design.
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| Toxicity/Toxicokinetics |
The toxicological profile of hydrocotarnine has not been extensively characterized. As a naturally occurring alkaloid and metabolite of noscapine, it is likely to have a moderate safety profile, but comprehensive toxicity studies are limited. The compound is intended for research use only and not for human therapeutic applications. In animal studies, hydrocotarnine at 10 mg/kg/day for 9 days was well-tolerated in mice. However, the compound's effects at higher doses or with longer duration of treatment have not been fully investigated. Researchers should follow standard laboratory safety practices and conduct appropriate toxicity assessments when using this compound in experimental studies.
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| References |
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| Additional Infomation |
4-Methoxy-6-methyl-7,8-dihydro-5H-[1,3]dioxacyclopenteno[4,5-g]isoquinoline is a type of isoquinoline compound. Hydrogenated theobromine has been reported in Corydalis ophiocarpa, Corydalis ochotensis, and Corydalis heterocarpa var. japonica, and relevant data are available for reference.
Hydrocotarnine serves as a valuable research tool for studying the SFK-Cbl axis and its role in regulating NLRP3 inflammasome activation. The compound's ability to induce inflammasome-mediated IL-18 secretion makes it useful for investigating inflammatory bowel disease mechanisms and potential therapeutic strategies. Its effects on GLUT1 expression and glucose uptake provide opportunities for studying glycolytic metabolism in immune cells. Hydrocotarnine's analgesic properties make it relevant for cancer pain research and studies on opioid analgesia. The compound is also valuable for natural product chemistry research as a tetrahydroisoquinoline alkaloid. |
| Molecular Formula |
C12H15NO3
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|---|---|
| Molecular Weight |
221.25200
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| Exact Mass |
221.105
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| CAS # |
550-10-7
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| PubChem CID |
3646
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| Appearance |
Light yellow to yellow solid
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| Boiling Point |
342.4ºC at 760 mmHg
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| Melting Point |
55.5 - 56.5 °C
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| Flash Point |
106.7ºC
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| LogP |
1.349
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
16
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| Complexity |
261
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCC2=CC3=C(C(=C2C1)OC)OCO3
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| InChi Key |
XXANNZJIZQTCBP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H15NO3/c1-13-4-3-8-5-10-12(16-7-15-10)11(14-2)9(8)6-13/h5H,3-4,6-7H2,1-2H3
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| Chemical Name |
4-methoxy-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinoline
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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 : ≥ 100 mg/mL (~451.98 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.30 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 (11.30 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (11.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.5198 mL | 22.5989 mL | 45.1977 mL | |
| 5 mM | 0.9040 mL | 4.5198 mL | 9.0395 mL | |
| 10 mM | 0.4520 mL | 2.2599 mL | 4.5198 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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