| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Phosphodiesterase 4 (PDE4) - selective, non-competitive inhibitor [1]
Ki (PDE4) = 3.4 μM [1] IC50 (PDE4) ≈ 3.16 μM (from -log IC50 ~5.5) [1] High-affinity rolipram binding site (weak affinity) [1] IC50 (displacement) ≈ 100 μM (from -log IC50 = 4.04 ± 0.06) [1] Calcium channels (benzothiazepine site) - antagonist [1] α-adrenoceptors - non-competitive antagonist [1] |
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| ln Vitro |
Relaxation of Human Bronchus: Glaucine (0.1 μM - 1 mM) caused concentration-dependent relaxation of both spontaneous and histamine (0.1 mM)-induced tone in human isolated bronchus. pD2 values were 4.58 ± 0.04 (spontaneous tone) and 4.49 ± 0.05 (histamine-induced tone). Maximal relaxation was 92.6 ± 1.3% and 87.8 ± 1.2% of theophylline (1 mM) response, respectively. [1]
Calcium Antagonist Activity: Glaucine (0.01-1 mM) depressed contractile responses to Ca²⁺ in K⁺-depolarized human bronchus in a concentration-dependent manner (pD₂ = 3.62 ± 0.06). It reduced the sustained rise of [Ca²⁺]i produced by histamine (100 μM) in cultured human airway smooth muscle cells with -log IC50 = 4.31 ± 0.07, while scarcely affecting the initial peak response. [1] Effect on β-Adrenoceptor Responses: Glaucine (10 μM) did not potentiate isoprenaline-induced relaxation of human bronchus but augmented isoprenaline-stimulated cyclic AMP accumulation (from 29.7 ± 3.1 to 45.2 ± 3.9 pmol/mg protein). [1] PKA Independence in Bronchus: The relaxant effect of glaucine was resistant to H-89 (5 μM), a selective PKA inhibitor, whereas forskolin-induced relaxation was antagonized. [1] Effects on Human Polymorphonuclear Leukocytes: Glaucine (10 μM) augmented cyclic AMP levels in FMLP-activated PMNs (from 432 ± 22 to 876 ± 35 fmol/10⁶ cells) and enhanced isoprenaline-stimulated cAMP accumulation. It inhibited FMLP-induced superoxide generation (-log IC50 = 4.76 ± 0.17), elastase release (-log IC50 = 3.53 ± 0.03), LTB₄ production (-log IC50 = 5.85 ± 0.07), [Ca²⁺]i signal (AUC, -log IC50 = 4.22 ± 0.03), and platelet aggregation (-log IC50 = 3.43 ± 0.05). It also inhibited superoxide release induced by A23187 (-log IC50 = 5.13 ± 0.19), PMA (-log IC50 = 3.87 ± 0.04), and SOZ (-log IC50 = 3.60 ± 0.07). The inhibitory effect on FMLP-induced superoxide was reduced by H-89. [1] Effects on Human Eosinophils: Glaucine (up to 3 mM) scarcely affected SOZ-induced superoxide generation but inhibited FMLP-induced eosinophil peroxidase release with -log IC50 = 3.74 ± 0.17. [1] |
| Enzyme Assay |
PDE Activity Assay (Human Bronchus and PMNs): Human bronchial tissue or PMNs were homogenized and centrifuged. The supernatant was applied to a Mono-Q HR 5/5 column attached to an FPLC system. PDE isoenzymes were eluted against a sodium acetate gradient (50-1000 mM). PDE activity was assayed using the method of Thompson & Strada (1984). The incubation mixture (400 μL) contained Tris-HCl 40 mM, MgCl₂ 5 mM, β-mercaptoethanol 3.75 mM, 1 μM ³H-labeled/unlabeled cyclic nucleotide (~200,000 d.p.m.), and glaucine. The assay was initiated by adding 100 μL enzyme solution and carried out at 30°C for 20 min. PDE3 and PDE4 activities were determined in the presence of 10 μM rolipram and 10 μM SKF94120, respectively. Glaucine selectively inhibited PDE4 with IC50 ~3.16 μM (from -log IC50 ~5.5). Kinetic analysis (Lineweaver-Burk and Dixon plots) showed non-competitive inhibition with Ki = 3.4 μM. [1]
[³H]-Rolipram Binding Assay (Rat Brain Cortex): Rat brain cortex membranes were prepared and incubated with [³H]-rolipram and various concentrations of glaucine (at least six concentrations in duplicate) to generate displacement curves. Glaucine displaced [³H]-rolipram from its high-affinity binding site with -log IC50 = 4.04 ± 0.06 (IC50 ≈ 100 μM). [1] |
| Cell Assay |
Human Bronchial Ring Relaxation Assay: Bronchial rings (2-4 mm diameter) from patients undergoing lung surgery were suspended in organ baths containing Krebs solution (37°C, 5% CO₂ in O₂, pH 7.4) for isometric recording. Preparations were initially challenged with ACh (1 mM) to determine maximal contractile response. Cumulative concentrations of glaucine (0.1 μM - 1 mM) were added to preparations with spontaneous tone or precontracted with histamine (0.1 mM). Theophylline (1 mM) was added at the end to represent maximal relaxation. [1]
Calcium Antagonist Assay: Preparations were equilibrated with K⁺-rich (40 mM), Ca²⁺-free medium. Cumulative concentration-response curves to CaCl₂ were constructed in the absence and presence of glaucine (0.01-1 mM, 30 min preincubation). [1] Human Airway Smooth Muscle Cell [Ca²⁺]i Measurement: Primary cultures of human trachealis muscle cells were prepared and loaded with fluo-3/AM (2 μM). Histamine (100 μM) was added to cell suspensions, and fluorescence changes were monitored for 3 min in the absence and presence of glaucine (10-300 μM, 3 min incubation). [1] PMN Functional Assays: Human PMNs were isolated from blood by standard procedures. Cells were pre-incubated with glaucine (1 μM - 1 mM, 5-7 min) then stimulated with various agents. Superoxide generation was measured as SOD-inhibitable cytochrome c reduction. Elastase release was measured spectrofluorometrically. LTB₄ was quantified by enzyme immunoassay. [Ca²⁺]i was measured in fluo-3/AM-loaded cells. Platelet aggregation in a PMN-platelet system was measured with an aggregometer. [1] Eosinophil Functional Assays: Eosinophils were isolated from PMN preparations by magnetic cell separation using anti-CD16 coated microbeads. Superoxide generation (SOZ stimulation) and eosinophil peroxidase release (FMLP stimulation) were measured. [1] Cyclic AMP Measurement: Bronchial rings or PMNs were incubated with glaucine (10 μM) and/or isoprenaline (10 μM) or FMLP (1 μM). Cyclic AMP was extracted and quantified by enzyme immunoassay kit. [1] |
| Toxicity/Toxicokinetics |
Clinical Safety Profile: The study notes that glaucine has been used clinically as a remedy for cough and other illnesses. The very low PDE4/binding site ratio (PDE4 IC50/binding IC50 ≈ 0.04) may account for the absence of vomiting in its past clinical use (Dierckx et al., 1981). [1]
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| References |
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| Additional Infomation |
(S)-Glaucin is an apophene alkaloid with the chemical formula (S)-1,2,9,10-tetrahydroxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, in which the four phenolic hydroxyl hydrogens are replaced by methyl groups. It possesses various pharmacological activities, including inhibition of platelet aggregation, inhibition of NF-κB, antitussive, antibacterial, muscle relaxant, and antitumor effects. It is also a metabolite in plants and rodents. It is an apophene alkaloid, polyether, organic heterotetracyclic compound, and tertiary amine compound, and is the conjugate base of (S)-Glaucin(1+). Glaucin has been reported to be found in Platycapnos tenuiloba, Neolitsea parvigemma, and other organisms with relevant data.
Background and Source: Glaucine [S-(+)-1,2,9,10-tetramethoxyaporphine] is an alkaloid isolated from the plant Glaucium flavum Crantz (Papaveraceae). It is a tetrahydroisoquinoline derivative structurally related to papaverine. It has been used for years as a remedy for cough and other illnesses. [1] Mechanism of Action - Dual Activity: Glaucine exhibits a dual mechanism of action depending on the tissue: [1] In human bronchus, calcium channel antagonism (benzothiazepine site) appears mainly responsible for its relaxant effect. [1] In human granulocytes (PMNs, eosinophils), PDE4 inhibition and interference with calcium entry contribute to its inhibitory effects on functional responses. [1] PDE4 Selectivity and Binding Profile: Glaucine is a relatively selective, non-competitive inhibitor of PDE4 with very low affinity for the high-affinity rolipram binding site. This results in an extremely low PDE4/binding site ratio (~0.04), which is of potential interest for asthma therapy as it may be associated with reduced emetic side effects compared to first-generation PDE4 inhibitors like rolipram. [1] Clinical Relevance in Asthma: The combination of bronchodilator (calcium antagonist) and anti-inflammatory (PDE4 inhibition) properties makes glaucine an attractive compound for asthma treatment. The study suggests that further structure-activity studies could identify more potent PDE4 inhibitors with less contribution from other activities. [1] |
| Molecular Formula |
C21H25NO4
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|---|---|
| Molecular Weight |
355.43
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| Exact Mass |
355.178
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| CAS # |
475-81-0
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| PubChem CID |
16754
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| Appearance |
White to light brown solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
487.0±45.0 °C at 760 mmHg
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| Melting Point |
246-247ºC
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| Flash Point |
140.2±25.9 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.576
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| LogP |
3.86
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
489
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1CCC2=CC(=C(C3=C2[C@@H]1CC4=CC(=C(C=C43)OC)OC)OC)OC
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| InChi Key |
RUZIUYOSRDWYQF-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C21H25NO4/c1-22-7-6-12-9-18(25-4)21(26-5)20-14-11-17(24-3)16(23-2)10-13(14)8-15(22)19(12)20/h9-11,15H,6-8H2,1-5H3/t15-/m0/s1
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| Chemical Name |
(6aS)-1,2,9,10-tetramethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
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| Synonyms |
Glaucine d-Glaucine Bromcholitin
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~281.35 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.03 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 (7.03 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8135 mL | 14.0675 mL | 28.1349 mL | |
| 5 mM | 0.5627 mL | 2.8135 mL | 5.6270 mL | |
| 10 mM | 0.2813 mL | 1.4067 mL | 2.8135 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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