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Costunolide [also known as (+)-Costunolide, Costus lactone, CCRIS-6754 and NSC-106404] is a naturally occurring sesquiterpene compound with a wide spectrum of biological activities such as anti-inflammatory, anticancer, antidiabetic, antiviral, antimicrobial, antiulcer, antifungal, antioxidant, and anthelmintic properties. It was initially discovered in 1960 in Saussurea costus roots. With an IC50 of 20 μM, costunolide inhibits FPTase. It also inhibits telomerase, with an IC50 of 65-90 μM.
Physicochemical Properties
| Molecular Formula | C15H20O2 | |
| Molecular Weight | 232.32 | |
| Exact Mass | 232.146 | |
| Elemental Analysis | C, 77.55; H, 8.68; O, 13.77 | |
| CAS # | 553-21-9 | |
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| PubChem CID | 5281437 | |
| Appearance | White to yellow solid powder | |
| Density | 1.0±0.1 g/cm3 | |
| Boiling Point | 385.4±42.0 °C at 760 mmHg | |
| Melting Point | 106 °C | |
| Flash Point | 162.0±25.3 °C | |
| Vapour Pressure | 0.0±0.9 mmHg at 25°C | |
| Index of Refraction | 1.519 | |
| LogP | 4.05 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 2 | |
| Rotatable Bond Count | 0 | |
| Heavy Atom Count | 17 | |
| Complexity | 401 | |
| Defined Atom Stereocenter Count | 2 | |
| SMILES | O=C(O[C@@]1([H])[C@@]2([H])CC/C(C)=C/CC/C(C)=C/1)C2=C |
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| InChi Key | HRYLQFBHBWLLLL-AHNJNIBGSA-N | |
| InChi Code | InChI=1S/C15H20O2/c1-10-5-4-6-11(2)9-14-13(8-7-10)12(3)15(16)17-14/h5,9,13-14H,3-4,6-8H2,1-2H3/b10-5+,11-9+/t13-,14+/m0/s1 | |
| Chemical Name | (3aS,6E,10E,11aR)-6,10-dimethyl-3-methylidene-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-2-one | |
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| 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | FPTase ( IC50 = 20 μM ); Telomerase (MDA-MB-231) ( IC50 = 65 μM ); Telomerase (MCF-7) ( IC50 = 90 μM ) | ||
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| ln Vivo |
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| Enzyme Assay | The TRAP assay measures telomerase activity using the TRAPez Telomerase Detection Kit, which contains primers for a 36-bp internal control (IC) that allows the amplification of telomerase activity to be quantified within a linear range near 2.5 logs. To treat the extract with RNase, 10μL of it are incubated for 20 minutes at 37 °C with 1μg of RNase. The TRAP assay products are separated by electrophoresis in a nondenaturing 12% PAGE with a buffer that contains 0.5 × Tris-borate EDTA, and they are then autoradiographically detected. Dried gels are exposed to room temperature Fuji Imaging Plates in order to quantify TRAP products. The untreated control cell signal is assigned a standard value of 100 after background correction is applied to the results. The signal intensities of cells treated with costunolide are expressed as a percentage of the maximum value of 100 and are compared to the standard.[1] | ||
| Cell Assay | 1) In a 96-well plate, plate 500–10,000 cells with 200 μL of media per well. 8 wells should be left empty for blank controls. 2) To enable the cells to adhere to the wells, incubate (37 °C, 5% CO2) for the entire night. 3) Fill each well with 2 μL of dissolved costunolide in DMSO. To ensure that the samples and media are well mixed, place on a shaking table and shake for five minutes at 150 rpm. 5) Allow Costunolide to work for 48 hours by incubating at 37 °C with 5% CO2. 6) Add at least 2 milliliters (mL) of MTT solution (5 mg/mL) to each 96-well plate in PBS. Since MTT in solution is not long-term stable, do not create a stock. 7) Fill each well with 20 μL of MTT solution. Put the media on a shaking table and spin it at 150 rpm for five minutes to fully incorporate the MTT. 8) Let the MTT metabolize for one to five hours by incubating at 37 °C with 5% CO2. 9) Dismiss the press. (If needed, dry the plate on paper towels to get rid of any residue. The MTT metabolic product, formazan, should be redissolved in 200 μL of DMSO. To completely combine the formazan and solvent, put on a shaking table and shake for five minutes at 150 rpm. 11) Determine the optical density at 560 nm. 11) Subtract background at 670 nm and read optical density at 560 nm. There should be a direct relationship between cell quantity and optical density. | ||
| Animal Protocol |
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| References |
[1]. Cancer Lett . 2005 Sep 28;227(2):153-62. [2]. Planta Med . 2001 Jun;67(4):358-9. [3]. Biol Pharm Bull . 2001 Mar;24(3):303-6. [4]. BMC Complement Altern Med . 2012 Mar 7:12:13. [5]. Cancer Lett . 2002 Dec 10;187(1-2):129-33. |
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| Additional Infomation |
Costunolide is a germacranolide with anthelminthic, antiparasitic and antiviral activities. It has a role as an anthelminthic drug, an antiinfective agent, an antineoplastic agent, an antiparasitic agent, an antiviral drug and a metabolite. It is a germacranolide and a heterobicyclic compound. (+)-Costunolide has been reported in Ainsliaea uniflora, Frullania tamarisci, and other organisms with data available. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.76 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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 (10.76 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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 3: ≥ 2.5 mg/mL (10.76 mM) (saturation unknown) in 10% EtOH + 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 EtOH stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: ≥ 2.08 mg/mL (8.95 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 20.8 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 5: ≥ 2.08 mg/mL (8.95 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 20.8 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 6: ≥ 2.08 mg/mL (8.95 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 7: 2% DMSO +Corn oil : 10 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3044 mL | 21.5220 mL | 43.0441 mL | |
| 5 mM | 0.8609 mL | 4.3044 mL | 8.6088 mL | |
| 10 mM | 0.4304 mL | 2.1522 mL | 4.3044 mL |