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| Targets |
Thiocolchicine-d3 targets microtubules by binding to tubulin, specifically the colchicine-binding site on β-tubulin. It functions as a microtubule polymerization inhibitor that disrupts the dynamic equilibrium of microtubule assembly and disassembly. This mechanism of action places the compound within the microtubule/tubulin pathway and the apoptosis pathway. By binding to tubulin heterodimers, Thiocolchicine prevents their incorporation into growing microtubules, leading to mitotic arrest and subsequent apoptosis in actively dividing cells. The deuterated analog is used as a tracer in studies of this pathway.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
In vitro, Thiocolchicine demonstrates potent inhibition of tubulin polymerization with an IC₅₀ of 2.5 µM. Competitive binding assays show that Thiocolchicine binds to tubulin with a Kᵢ of 0.7 µM, indicating high affinity for the colchicine-binding site. The compound exhibits antiproliferative activity against various cancer cell lines through disruption of the mitotic spindle and induction of G₂/M phase cell cycle arrest. The deuterated form, Thiocolchicine-d3, is employed as an internal standard in cell-based studies to accurately quantify intracellular drug concentrations and evaluate the pharmacokinetics of the non-deuterated compound. |
| ln Vivo |
Thiocolchicine-d3 is used in vivo as a deuterated internal standard for pharmacokinetic studies of Thiocolchicine. The non-deuterated parent compound has been studied for its antitumor activity in various preclinical models. As a microtubule inhibitor, Thiocolchicine induces mitotic catastrophe and apoptosis in tumor xenograft models. The compound's ability to bind tubulin with high affinity contributes to its in vivo efficacy. However, the deuterated form itself is not the primary pharmacologically active species but rather serves as an analytical tool to enable accurate quantification of parent drug concentrations in plasma and tissues during in vivo studies.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Thiocolchicine typically involve competition binding experiments using radiolabeled colchicine or fluorescent probes to assess binding affinity to tubulin. The standard protocol includes incubating purified tubulin with varying concentrations of Thiocolchicine, followed by measurement of bound ligand using scintillation counting or fluorescence polarization. IC₅₀ and Kᵢ values are calculated from dose-response curves. For the deuterated analog, it is used as an internal standard in LC-MS-based binding assays where the binding of the non-deuterated compound to tubulin is quantified using the deuterated species for mass spectrometric calibration.
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| Cell Assay |
Cell-based assays for Thiocolchicine involve culturing cancer cell lines (e.g., HeLa, A549, or MCF-7) and treating them with varying concentrations of the compound. Cell viability is assessed using MTT or CCK-8 assays after 48-72 hours of treatment. Cell cycle analysis by flow cytometry with propidium iodide staining reveals G₂/M phase arrest. Apoptosis is evaluated using Annexin V-FITC/PI double staining. For the deuterated form, cellular uptake and intracellular concentration are determined by LC-MS/MS analysis using the deuterated compound as an internal standard to quantify the non-deuterated parent compound in cell lysates.
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| Animal Protocol |
In vivo animal experiments for Thiocolchicine typically use rodent xenograft models (e.g., nude mice bearing human tumor xenografts). Animals are administered Thiocolchicine via intraperitoneal or intravenous injection at various doses. Tumor volume is measured periodically using calipers, and body weight is monitored for toxicity assessment. At study termination, plasma and tissue samples are collected for pharmacokinetic analysis. The deuterated analog, Thiocolchicine-d3, is used as an internal standard in the LC-MS/MS quantification of parent drug concentrations in these samples, enabling accurate determination of exposure and pharmacokinetic parameters.
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| ADME/Pharmacokinetics |
Thiocolchicine-d3 is used as an internal standard for pharmacokinetic studies of Thiocolchicine. Typical pharmacokinetic parameters of Thiocolchicine include moderate oral bioavailability, extensive tissue distribution due to its lipophilic nature, and hepatic metabolism. The compound shows rapid clearance in preclinical species. The deuterated form provides a mass shift of +3 Da relative to the non-deuterated compound, allowing simultaneous detection by mass spectrometry. Storage conditions for Thiocolchicine-d3 require protection from light at 4°C. Solubility is typically in DMSO, with in vivo formulation using DMSO:PEG300:Tween80:saline mixtures.
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| Toxicity/Toxicokinetics |
Toxicity data for Thiocolchicine-d3 as a deuterated internal standard are limited. The non-deuterated parent compound, Thiocolchicine, exhibits dose-dependent toxicity primarily due to its mechanism as a microtubule inhibitor affecting rapidly dividing cells in bone marrow and gastrointestinal epithelium. Standard precautions apply for handling. The compound is for research use only and not intended for human administration. Storage requires protection from light. No specific toxicological data are available for the deuterated form, which is used in trace quantities as an analytical standard.
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| References |
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| Additional Infomation |
Thiocolchicine-d3 (CAS 1314417-95-2) is a stable isotope-labeled research compound supplied for analytical and research purposes only. It is not a clinically approved drug and has no marketing authorization. The compound is a deuterated substitute of Thiocolchicine, which itself is an analog of colchicine. Thiocolchicine can serve as a toxin molecule for ADC development. The compound should be stored at 4°C protected from light. Purity is typically >98%. The deuterium labeling is at the N-acetyl methyl group.
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| Molecular Formula |
C22H25NO5S
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| Molecular Weight |
415.502605199814
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| Exact Mass |
418.164
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| CAS # |
1314417-95-2
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| Related CAS # |
Thiocolchicine;2730-71-4
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| PubChem CID |
53312028
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| Appearance |
White to off-white solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
744
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O(C1C(=C(OC)C=C2CC[C@H](NC(=O)C([H])([H])[H])C3=CC(=O)C(SC)=CC=C3C=12)OC)C
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| InChi Key |
CMEGANPVAXDBPL-AVSFSGARSA-N
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| InChi Code |
InChI=1S/C22H25NO5S/c1-12(24)23-16-8-6-13-10-18(26-2)21(27-3)22(28-4)20(13)14-7-9-19(29-5)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m0/s1/i1D3
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| Chemical Name |
2,2,2-trideuterio-N-[(7S)-1,2,3-trimethoxy-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 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.4067 mL | 12.0337 mL | 24.0674 mL | |
| 5 mM | 0.4813 mL | 2.4067 mL | 4.8135 mL | |
| 10 mM | 0.2407 mL | 1.2034 mL | 2.4067 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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