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| Targets |
3-Demethylthiocolchicine targets tubulin, the protein subunit of microtubules, similar to colchicine. It binds to the colchicine binding site on beta-tubulin, inhibiting microtubule polymerization and disrupting the mitotic spindle. This leads to cell cycle arrest at the G2/M phase and induction of apoptosis in rapidly dividing cells. It has the same effects and activities as colchicine in microtubule binding, blocking casein-induced amyloidosis, and anti-inflammatory effects, with significantly lower toxicity.
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| ln Vitro |
3-Demethylthiocolchicine has the same in vitro activities as colchicine, including inhibition of microtubule polymerization, anti-inflammatory effects, and blocking of casein-induced amyloidosis. As a tubulin-binding agent, it disrupts the cytoskeleton and inhibits cell proliferation in cancer cell lines. The exact IC50 values for various cancer cell lines are not provided, but its broad-spectrum antitumor activity indicates potent anti-proliferative effects at low micromolar concentrations.
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| ln Vivo |
Specific in vivo activity data for 3-Demethylthiocolchicine is not provided in the search results. However, as a colchicine analog with broad-spectrum antitumor activity, it would be expected to show anti-tumor efficacy in xenograft mouse models of various cancers (e.g., breast, lung, colon). Its significantly lower toxicity compared to colchicine suggests a potential for a wider therapeutic window in vivo for certain indications such as amyloidosis or inflammation.
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| Enzyme Assay |
The binding of 3-Demethylthiocolchicine to tubulin can be assessed using a tubulin polymerization assay. Procedure: Purified bovine brain tubulin (3 mg/mL) is dissolved in ice-cold PEM buffer (80 mM PIPES, pH 6.9, 1 mM EGTA, 1 mM MgCl2, 1 mM DTT, 10% glycerol) in a 96-well half-area plate. Varying concentrations of 3-Demethylthiocolchicine (0.1-100 uM) are added. The plate is warmed to 37degC, and absorbance at 340 nm is measured every minute for 60 minutes. The slope of the absorbance curve indicates the rate of tubulin polymerization. Inhibition of polymerization is calculated compared to control (DMSO). Colchicine (10 uM) is used as a positive control.
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| Cell Assay |
A cell proliferation assay can be performed using various cancer cell lines (e.g., HeLa, A549, MCF-7, HCT116). Procedure: Cells are seeded in 96-well plates at 5x103 cells/well and allowed to attach overnight. Cells are treated with serial dilutions of 3-Demethylthiocolchicine (0.1-100 uM) for 72 hours. Cell viability is measured using the MTT assay or CellTiter-Glo luminescent assay. The IC50 is calculated from dose-response curves. For cell cycle analysis, cells are treated with the compound (e.g., 1-10 uM) for 24 hours, stained with propidium iodide, and analyzed by flow cytometry to assess G2/M arrest.
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| Animal Protocol |
In vivo efficacy can be evaluated in a mouse xenograft model of human cancer. Procedure: 6-8 week old female athymic nude mice are inoculated subcutaneously with 5x10⁶ cancer cells (e.g., HeLa or A549) in Matrigel. When tumors reach 100-150 mm3, mice are randomized into groups (n=8-10). 3-Demethylthiocolchicine is dissolved in a suitable vehicle (e.g., 5% DMSO, 40% PEG300, 55% saline) and administered intraperitoneally at doses of 1, 3, and 10 mg/kg once daily for 14-21 days. Tumor volumes are measured every 2-3 days with calipers. Body weight is monitored for toxicity. At study endpoint, tumors are harvested for histology and analysis of proliferation (Ki-67) and apoptosis (TUNEL).
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| ADME/Pharmacokinetics |
Specific PK data for 3-Demethylthiocolchicine is not provided. As a colchicine analog, it is likely to be absorbed after oral administration but may have a narrow therapeutic window. It is expected to be distributed to tissues (including the liver and kidneys) and metabolized primarily by CYP3A4. Its half-life in humans may be similar to colchicine (approximately 20-40 hours). The significantly lower toxicity compared to colchicine suggests improved pharmacokinetic or pharmacodynamic properties.
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| Toxicity/Toxicokinetics |
3-Demethylthiocolchicine has significantly lower toxicity compared to colchicine while retaining its beneficial effects on microtubule binding, anti-inflammatory activity, and inhibition of amyloidosis. This improved safety profile makes it an attractive research tool for studying tubulin-targeting therapies with reduced side effects. However, colchicine and its analogs are known to be toxic at high doses, and handling should follow standard safety precautions for cytotoxic compounds (use of gloves, fume hood, and proper disposal).
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| References |
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| Additional Infomation |
See the first source for RN and structural formulas; RN is not included in Chemline 10/85. See the first source for structural formulas.
3-Demethylthiocolchicine is a colchicine analog with broad-spectrum antitumor activity and significantly lower toxicity than colchicine. It retains the same microtubule-binding, anti-inflammatory, and anti-amyloidosis effects as colchicine. The compound is also a degradation product of thiocolchicoside and is used as an impurity standard for thiocolchicoside analysis. It appears as a solid powder with a purity of ≥95%. This product is for research use only and is not an approved drug. |
| Molecular Formula |
C21H23NO5S
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|---|---|
| Molecular Weight |
401.48
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| Exact Mass |
401.13
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| CAS # |
87424-25-7
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| PubChem CID |
84076
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| Appearance |
Solid Powder
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| Density |
1.33g/cm3
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| Boiling Point |
769ºC at 760 mmHg
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| Melting Point |
>240ºC (dec.)
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| Flash Point |
418.9ºC
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| Index of Refraction |
1.636
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| LogP |
3.673
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
728
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(=O)NC1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)SC)OC)OC)O
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| InChi Key |
PKYOHQGXPPVIGD-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C21H23NO5S/c1-11(23)22-15-7-5-12-9-17(25)20(26-2)21(27-3)19(12)13-6-8-18(28-4)16(24)10-14(13)15/h6,8-10,15,25H,5,7H2,1-4H3,(H,22,23)/t15-/m0/s1
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| Chemical Name |
N-[(7S)-3-hydroxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
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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 : ~125 mg/mL (~311.35 mM; with ultrasonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4908 mL | 12.4539 mL | 24.9078 mL | |
| 5 mM | 0.4982 mL | 2.4908 mL | 4.9816 mL | |
| 10 mM | 0.2491 mL | 1.2454 mL | 2.4908 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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