| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
Linderalactone targets multiple cellular pathways critical for cancer cell survival and proliferation. Its primary mechanism of action involves the inhibition of the JAK/STAT signaling pathway, a key regulator of cell growth, differentiation, and apoptosis. Additionally, it modulates the expression of apoptosis-related proteins, specifically by downregulating the anti-apoptotic protein Bcl-2 and upregulating the pro-apoptotic protein Bax. This shift in the Bax/Bcl-2 ratio promotes the intrinsic apoptotic pathway. The compound also induces G2/M phase cell cycle arrest, further contributing to its antiproliferative effects. Furthermore, Linderalactone has been shown to inhibit superoxide anion generation in human neutrophils, indicating potential anti-inflammatory properties through the modulation of reactive oxygen species production.
|
|---|---|
| ln Vitro |
A549 cells treated with suspension doses for 24 hours showed growth inhibition from endomelide (0-100 μM). Hegenolide's IC50 is 15 μM[1]. Treatment of A549 cells with linderalactone (7.5-30 μM) causes cell fluorescence. A549 cells are treated with linderalactone (7.5-30 μM; 24 hours) to trigger the G2/M cell cycle. A549 cells are anesthetized by linderalactone (7.5–30 μM), which works in a dose-dependent manner[1]. suppresses the expression of JAK1, JAK2, and STAT1. Additionally, phosphorylation of pSTAT1, pSTAT-2, pJAK1, and pJAk2 can be inhibited by hierastrolide [1].
In vitro studies have demonstrated that Linderalactone exhibits significant antiproliferative activity against human lung cancer A-549 cells, with an IC50 value of 15 µM. This growth inhibition is attributed to its ability to modulate the expression of key apoptosis regulators, leading to programmed cell death. The compound also induces G2/M cell cycle arrest in these cancer cells, preventing further division and proliferation. Furthermore, Linderalactone shows significant inhibitory effects on superoxide anion generation by human neutrophils in response to fMLP/CB, with an IC50 of 8.48 µg/mL (approximately 34.7 µM), suggesting potent anti-inflammatory and antioxidant activities. These in vitro activities confirm its potential as a multi-targeted anticancer and anti-inflammatory agent. |
| ln Vivo |
Detailed in vivo activity data for Linderalactone are limited in the available literature. However, given its potent in vitro anticancer activity and its ability to modulate the JAK/STAT pathway and apoptosis, it is expected to have therapeutic potential in various in vivo tumor models. The compound's natural product origin and established biological activities make it a candidate for further preclinical evaluation. Studies involving xenograft models would be necessary to fully characterize its in vivo efficacy, pharmacokinetic profile, and therapeutic window. Its ability to inhibit superoxide anion generation also suggests potential for in vivo anti-inflammatory studies.
|
| Enzyme Assay |
Non-cell-based assays for Linderalactone typically involve enzyme inhibition studies to confirm its mechanism of action. For JAK/STAT pathway inhibition, kinase assays are performed using purified JAK kinases. The compound is incubated with the kinase, a peptide substrate, and ATP at varying concentrations. Kinase activity is measured by quantifying substrate phosphorylation using techniques such as radiometric detection, fluorescence polarization, or ELISA. IC50 values for JAK inhibition are determined from dose-response curves. Additionally, cell-free apoptosis assays may be used to assess the compound's direct effects on Bax and Bcl-2 protein interactions or conformational changes.
|
| Cell Assay |
Cell viability assay [1]
Cell Types: lung cancer A549 cells Tested Concentrations: 0 μM, 1]. 1.6 μM, 3.2 μM, 6.25 μM, 12.5 μM, 25 μM, 50 μM, 100 μM Incubation Duration: 24 hrs (hours) Experimental Results: Concentration-dependent inhibition of A549 cell growth. Apoptosis analysis [1] Cell Types: lung cancer A549 cells Tested Concentrations: 7.5 μM, 15 μM, 30 μM Incubation Duration: Experimental Results: Induced apoptosis of A549 cells in a dose-dependent manner. Cell cycle analysis [1] Cell Types: Lung cancer A549 cells Tested Concentrations: 7.5 μM, 15 μM, 30 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced G2/M cell cycle arrest. Western Blot Analysis [1] Cell Types: lung cancer A549 cells Tested Concentrations: 7.5 μM, 15 μM, 30 μM Incubation Duration: Experimental Results: Inhibition of JAK/STAT pathway in A549 cells. Cellular assays for Linderalactone are performed in cancer cell lines such as A-549 human lung adenocarcinoma cells. Cells are cultured in appropriate medium and treated with the compound at various concentrations (typically ranging from 7.5 to 30 µM). Following treatment for specified durations (e.g., 16-72 hours), cell proliferation and viability are assessed using standard assays such as MTT, CCK-8, or CellTiter-Glo to determine the IC50 for growth inhibition. Cell cycle analysis is performed by flow cytometry after propidium iodide staining to confirm G2/M arrest. Apoptosis is evaluated using Annexin V/PI staining or by measuring caspase activity. Protein expression changes (Bax, Bcl-2, JAK/STAT components) are analyzed by Western blotting. |
| Animal Protocol |
In vivo animal models for Linderalactone would be required to assess its therapeutic potential. Standard protocols would involve xenograft studies in immunodeficient mice bearing human tumor cell lines such as A-549. The compound would be administered via oral gavage or intraperitoneal injection at various doses, formulated using appropriate vehicles (e.g., DMSO, PEG300, Tween 80, or CMC-Na). Tumor growth inhibition would be monitored by caliper measurements over time. Pharmacodynamic markers such as JAK/STAT pathway activity, Bax/Bcl-2 expression, and apoptosis markers in tumor tissues would be assessed by Western blotting or immunohistochemistry. Toxicity and body weight changes would also be monitored. Detailed protocols are not extensively reported in the available literature.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Linderalactone include a molecular weight of 244.29 g/mol and molecular formula C15H16O3. The compound is soluble in DMSO (49 mg/mL) and ethanol (49 mg/mL) but is insoluble in water. For in vivo administration, it can be formulated as a homogeneous suspension in CMC-Na at concentrations up to 5 mg/mL. Detailed PK parameters such as half-life, bioavailability, volume of distribution, and clearance are not extensively reported in the available literature. The compound is a small molecule natural product with moderate lipophilicity, which may influence its absorption and distribution. Storage conditions: powder at -20°C for 3 years.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for Linderalactone are not extensively reported in the available literature. As a naturally occurring sesquiterpene lactone, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied as a high-purity research reagent (>99%) for laboratory use only. In vivo studies would be required to determine the maximum tolerated dose (MTD), LD50, and potential organ-specific toxicities. Given its mechanism of action involving apoptosis induction and cell cycle arrest, careful evaluation of effects on rapidly dividing normal tissues (e.g., bone marrow, gastrointestinal epithelium) would be necessary.
|
| References |
|
| Additional Infomation |
Linderalactone has been reported to be found in Neolitsea zeylanica, Neolitsea hiiranensis, and other organisms with available data.
Linderalactone is also known by its IUPAC name and is cataloged under CAS number 728-61-0. It is a natural product found in Neolitsea daibuensis and Radix Linderae (Lindera aggregata). The compound has a purity of 99.9% and is used for research purposes only. It is a furanogermacrane-type sesquiterpene lactone with mid-potency JAK/STAT inhibition, making it valuable for rigorous SAR and mechanistic studies. Its biological activities include anticancer effects through apoptosis modulation and JAK/STAT pathway inhibition, as well as inhibition of superoxide anion generation. References for its activity include studies by Chen K S et al. (Nat Prod Res, 2005) and Shu J N et al. (Chinese Journal of Modern Drug Application, 2009). |
| Molecular Formula |
C15H16O3
|
|---|---|
| Molecular Weight |
244.2857
|
| Exact Mass |
244.109
|
| CAS # |
728-61-0
|
| PubChem CID |
6450191
|
| Appearance |
White to yellow solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
437.9±45.0 °C at 760 mmHg
|
| Flash Point |
218.6±28.7 °C
|
| Vapour Pressure |
0.0±1.1 mmHg at 25°C
|
| Index of Refraction |
1.572
|
| LogP |
3.27
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
0
|
| Heavy Atom Count |
18
|
| Complexity |
422
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C/C/1=C\CCC2=C[C@H](C3=C(C1)OC=C3C)OC2=O
|
| InChi Key |
LWCKQMHMTSRRAA-QGQQYVBWSA-N
|
| InChi Code |
InChI=1S/C15H16O3/c1-9-4-3-5-11-7-13(18-15(11)16)14-10(2)8-17-12(14)6-9/h4,7-8,13H,3,5-6H2,1-2H3/b9-4+/t13-/m1/s1
|
| Chemical Name |
(1R,8E)-3,8-dimethyl-5,14-dioxatricyclo[10.2.1.02,6]pentadeca-2(6),3,8,12(15)-tetraen-13-one
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~136.44 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (10.23 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.23 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0935 mL | 20.4675 mL | 40.9350 mL | |
| 5 mM | 0.8187 mL | 4.0935 mL | 8.1870 mL | |
| 10 mM | 0.4093 mL | 2.0467 mL | 4.0935 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
