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| Other Sizes |
| Targets |
Indoleamine 2,3-dioxygenase 1 (IDO-1). Palmatine chloride is an orally active and irreversible IDO-1 inhibitor with IC50 values of 3 μM against HEK 293-hIDO-1 and 157 μM against recombinant human IDO-1. IDO-1 is an enzyme that catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism. By depleting tryptophan and producing kynurenine, IDO-1 suppresses immune responses and promotes immune tolerance. IDO-1 is often overexpressed in tumors, contributing to immune evasion. By inhibiting IDO-1, Palmatine chloride can restore immune function and enhance anti-tumor immunity. The compound also inhibits acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are enzymes that break down acetylcholine in the nervous system. Palmatine chloride and its analogues have been reported to exert a wide spectrum of pharmacological effects, including anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, antibacterial, antiviral, and regulating blood lipids.
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| ln Vitro |
Palmatin (0-100 μM; 42 h) diminishes the viral titers of DENV-2 and YFV with EC50 values of 26.4 μM and 7.3 μM, respectively, and suppresses WNV with an EC50 value of 3.6 μM [3]. The growth of colon cancer cells is inhibited by palmatin (0-1128 μM; 24-72 hours) [5]. By means of mitochondria-related pathways, palmatin (0-704 μM; 24 hours) can cause AURKA protein levels to drop, G2/M phase arrest, and death in colon cancer cells [5].
Palmatine chloride is an orally active and irreversible IDO-1 inhibitor with IC50 values of 3 μM against HEK 293-hIDO-1 and 157 μM against recombinant human IDO-1. The compound also inhibits AChE and BChE. Palmatine chloride and its analogues have been reported to exert a wide spectrum of pharmacological effects, including anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, antibacterial, antiviral, and regulating blood lipids. The compound's IDO-1 inhibitory activity makes it a potential candidate for cancer immunotherapy. Its AChE and BChE inhibitory activity suggests potential applications in neurodegenerative diseases such as Alzheimer's disease. Palmatine chloride's diverse biological activities make it a valuable tool for studying multiple disease pathways. |
| ln Vivo |
Oral palmatine (50 or 100 mg/kg; given once daily for 7 days) reduces the infiltration of inflammatory cells and ameliorates colitis caused by dextran sulfate sodium (DSS) [1]. ?In mice, fulminant liver failure produced by lipopolysaccharide and D-galactosamine can be lessened by intraperitoneal injection of palmatin (0-200 mg/kg) once [2]. ?In mice, palmatine (0–1 mg/kg; i.p.; 10 days) has memory-improving effects [4]. ?The growth of HCT-116 xenografts in mice is successfully inhibited by palmatine (33.75–135 mg/kg; oral; once daily for 26 days) [5].
Palmatine chloride has been studied in vivo for its various pharmacological effects. As an orally active IDO-1 inhibitor, it has the potential to modulate immune responses and enhance anti-tumor immunity. The compound's anti-cancer, anti-inflammatory, neuroprotective, and metabolic effects have been evaluated in preclinical models. Palmatine chloride has been shown to exert beneficial effects in models of cancer, infectious diseases, and metabolic disorders. Detailed in vivo pharmacokinetic and pharmacodynamic data are available from published studies. The compound is for research use only and is not for human therapeutic use. |
| Enzyme Assay |
IDO-1 enzyme activity assays are performed using recombinant human IDO-1 or IDO-1 from cell lysates. The enzyme is incubated with the substrate L-tryptophan in assay buffer (50 mM phosphate buffer pH 6.5, 20 mM ascorbate, 20 μg/mL catalase, 10 μM methylene blue) at 37°C for 30-60 minutes. The reaction product kynurenine is quantified by HPLC or by measuring absorbance at 321 nm after reaction with Ehrlich's reagent. Palmatine chloride is serially diluted in DMSO and added to the reaction mixture to determine IC50 values. AChE and BChE inhibition assays are performed using the Ellman's method. Each assay includes appropriate controls to validate the results.
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| Cell Assay |
Cell proliferation assay[5]
Cell Types: HCT-116, SW480, HT-29 Tested Concentrations: 0, 88, 176, 352 and 704 μM (HCT-116, SW480); 0, 141, 282, 564 and 1128 μM (HT -29) Incubation Duration: 24, 48 and 72 hrs (hours) Experimental Results: Cell viability diminished in a dose-dependent manner. Western Blot Analysis [5] Cell Types: HCT-116, SW480, HT-29 Tested Concentrations: 100 nM for HCT-116, 500 nM for SW480 and HT-29 Incubation Duration: 24 hrs (hours) Experimental Results: Promote the expression of apoptosis markers, For example, P53/P73, Caspase3 and Caspase9. AURKA protein levels are diminished. Cytochrome increases. c In the cytoplasm, both Bcl2 and Bcl-xl were diminished in a dose-dependent manner. Cell cycle analysis[5] Cell Types: HCT-116, SW480 Tested Concentrations: 88, 176, 352 and 704 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced G2/M phase arrest in a dose-dependent manner. Apoptosis analysis [5] Cell Types: HCT-116, SW480 Tested Concentrations: 88, 176, 352 and 704 μM Incubation Duration: 24 h Experimental Results: Apoptosis was induced in a dose-dependent manner. Cellular IDO-1 inhibition is evaluated in HEK 293 cells expressing human IDO-1 or in other IDO-1-expressing cell lines (e.g., HeLa cells stimulated with IFN-γ). Cells are cultured in appropriate media at 37°C with 5% CO₂ and treated with Palmatine chloride at concentrations ranging from 0.1 to 100 μM for 24-48 hours. IDO-1 activity in cell lysates or culture supernatants is assessed by measuring kynurenine levels by HPLC or using a colorimetric assay. AChE and BChE activity in cell lysates is assessed using the Ellman's method. Cell viability is assessed using MTT or LDH assays. Each experiment includes vehicle controls (DMSO) and appropriate positive controls (e.g., known IDO-1 inhibitors like 1-methyl-tryptophan). |
| Animal Protocol |
Animal/Disease Models: DSS-induced colitis BALB/c mouse model (8 weeks old) [1]
Doses: 50 or 100 mg/kg Route of Administration: Orally, daily, for 7 days Experimental Results: Improved DSS-induced colitis It also prevents the infiltration of inflammatory cells in colitis; Dramatically extends the length of the colon; and Dramatically inhibits colonic MPO activity. Reduce the levels of colon inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10); protect mucosal integrity by regulating TJs proteins and apoptotic proteins; restore DSS-induced Reduction of TJ proteins ZO-1, ZO-2 and Claudin-1; 100 mg/kg dose diminished Bax expression and enhanced Bcl-2 expression, preventing epithelial cell apoptosis and improving intestinal integrity. Preventing changes in intestinal microbiota in mice with DSS-induced colitis. Animal/Disease Models: Male ICR mouse (20-22 g), D-galactosamine/lipopolysaccharide (GalN/LPS)-induced fulminant liver failure model [2] Doses: 25, 50, 100 or 200 mg/kg given Medication: intraperitonealinj In vivo efficacy of Palmatine chloride is evaluated in various animal models of cancer, inflammation, neurodegenerative diseases, and metabolic disorders. The compound is administered orally or intraperitoneally at doses determined by preclinical studies. In cancer models, tumor growth is monitored, and immune cell infiltration and function are assessed. In models of neurodegenerative diseases, cognitive function and neuronal survival are assessed. In metabolic models, blood glucose and lipid levels are measured. Tissue samples are collected for histopathological analysis and biochemical assays (IDO-1 activity, kynurenine levels, AChE/BChE activity). Body weight and clinical signs are monitored throughout the study to assess tolerability. Sample sizes typically range from 6-10 animals per group. |
| ADME/Pharmacokinetics |
Molecular Weight: 387.86. Formula: C21H22ClNO4. CAS No.: 10605-02-4. IUPAC Name: 2,3,9,10-tetramethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium; chloride. Synonyms: Palmatine chloride; Palmatine hydrochloride; NSC-209407. Appearance: Solid. Purity: Typically ≥98%. Solubility: Soluble in DMSO and water. Storage: Typically at room temperature or -20°C. Palmatine chloride is an orally active IDO-1 inhibitor with a wide spectrum of pharmacological effects.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available for Palmatine chloride. The compound is intended for research use only and has not undergone full preclinical toxicology evaluation required for clinical development. As an IDO-1 inhibitor and cholinesterase inhibitor, potential toxicities may include effects on immune function and the nervous system. Standard toxicity studies would include acute toxicity assessment in rodents, repeated dose toxicity studies (14-day and 28-day), and genotoxicity screening (Ames test, micronucleus assay). The compound is for research use only and not for human therapeutic use.
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| References |
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| Additional Infomation |
Palmatine chloride is also known as Palmatine hydrochloride, NSC-209407, and Palmatine chloride salt. Its IUPAC name is 2,3,9,10-tetramethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium; chloride. Palmatine chloride is a protoberberine alkaloid found in various plants, including Berberis vulgaris and Coptidis rhizoma. It is an orally active and irreversible IDO-1 inhibitor with IC50 values of 3 μM against HEK 293-hIDO-1 and 157 μM against rhIDO-1. Palmatine chloride also inhibits AChE and BChE. The compound exerts a wide spectrum of pharmacological effects, including anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, antibacterial, antiviral, and regulating blood lipids. No clinical trials have been reported for this compound. Palmatine chloride is for research use only.
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| Molecular Formula |
C21H22CLNO4
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| Molecular Weight |
387.86
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| Exact Mass |
387.123
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| CAS # |
10605-02-4
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| Related CAS # |
Palmatine hydroxide;131-04-4;Palmatine;3486-67-7
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| PubChem CID |
73442
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| Appearance |
Light yellow to yellow solid powder
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| Melting Point |
205 °C
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| Vapour Pressure |
6.6E-15mmHg at 25°C
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| Index of Refraction |
1.624
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| LogP |
0.388
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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 |
27
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| Complexity |
475
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RLQYRXCUPVKSAW-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C21H22NO4.ClH/c1-23-18-6-5-13-9-17-15-11-20(25-3)19(24-2)10-14(15)7-8-22(17)12-16(13)21(18)26-4;/h5-6,9-12H,7-8H2,1-4H3;1H/q+1;/p-1
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| Chemical Name |
2,3,9,10-tetramethoxy-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium;chloride
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ≥ 32 mg/mL (~82.50 mM)
H2O : ~5 mg/mL (~12.89 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.45 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 (6.45 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 (6.45 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5782 mL | 12.8912 mL | 25.7825 mL | |
| 5 mM | 0.5157 mL | 2.5782 mL | 5.1565 mL | |
| 10 mM | 0.2578 mL | 1.2891 mL | 2.5782 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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