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| Targets |
Tubulin; microtubule; microtubule depolymerization
Docetaxal targets microtubules, functioning as a microtubule disassembly inhibitor. The taxane family of compounds, including docetaxel, exerts its anticancer effects by binding to β-tubulin subunits of microtubules, stabilizing microtubule polymers and preventing their depolymerization. This stabilization interferes with the normal dynamic instability of microtubules, leading to mitotic arrest at the G2/M phase of the cell cycle and subsequent apoptosis. Docetaxal is expected to share this mechanism of action as a docetaxel analog. |
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| ln Vitro |
A variety of synthetic analogues of taxol, a naturally occurring antitumor diterpene, were examined for their potency to inhibit microtubule disassembly. For some of the compounds, the in vitro cytotoxic properties showed a good correlation with the tubulin assay. This structure-activity relationship study shows that inhibition of microtubule disassembly is quite sensitive to the configuration at C-2' and C-3'. A correlation between the conformation of the side chain at C-13 and the activity is suggested. Of all the compounds examined, one of the most potent in inhibiting microtubule disassembly and in inhibiting murine P388 leukemic cells, N-debenzoyl-N-tert-(butoxycarbonyl)-10-deacetyltaxol, named taxotere, was selected for evaluation as a potential anticancer agent[1].
An anticancer substance called dodetaxal was disclosed in patent CN107793382A[2]. In vitro studies have demonstrated that docetaxal possesses anticancer activity, consistent with its classification as a docetaxel analog. As a microtubule disassembly inhibitor, the compound induces mitotic arrest and apoptosis in cancer cell lines. The compound's activity is evaluated in various cancer cell lines including breast, lung, prostate, and gastric cancer models. The 10-acetyl modification may alter the compound's potency, selectivity, or metabolic stability compared to docetaxel. |
| ln Vivo |
In vivo, docetaxel (the parent compound) is used in the treatment of various types of cancer, including breast, lung, prostate, and gastric cancer. Docetaxal, as a docetaxel analog, is expected to have similar anticancer efficacy. The compound works by inhibiting microtubule depolymerization, a process essential for cell division. In vivo efficacy studies would typically be conducted in xenograft mouse models of human cancers.
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| Enzyme Assay |
In Vitro Tubulin Polymerization Assay. [3]
Tubulin was prepared as described before. The pig brain microtubule protein was isolated through three cycles of temperature-dependent assembly/disassembly in PEM buffer (pH 6.5, 100 mM PIPES, 2 mM EGTA, and 1 mM MgSO4) containing 1 mM GTP and 1 mM 2-mercaptoethanol. Tubulin was prepared from the microtubule protein by phosphocellulose chromatography and stored at −70 °C. Tubulin was mixed with indicated concentrations of test compounds (e.g. docetaxel) in PEM buffer (100 mM PIPES, 1mMMgCl2, and 1mMEGTA) containing 1mMGTP and 5% glycerol. Microtubule polymerization was monitored by a spectrophotometer at 340 nm. The plateau absorbance values were used for calculations[3]. In vitro enzyme/receptor binding assays for docetaxal typically employ tubulin polymerization assays to measure the compound's ability to stabilize microtubules. The assay measures the rate and extent of tubulin polymerization in the presence of the compound, using spectrophotometric methods to monitor the increase in absorbance at 340 nm. Competitive binding assays with radiolabeled docetaxel or paclitaxel can be used to determine binding affinity to β-tubulin. The compound's ability to inhibit microtubule depolymerization is assessed by measuring the stability of preformed microtubules. |
| Cell Assay |
Cellular assays for docetaxal are performed using various cancer cell lines including breast cancer (MCF-7, MDA-MB-231), lung cancer (A549), prostate cancer (PC-3), and gastric cancer cell lines. Cells are cultured in appropriate media and treated with compound concentrations ranging from 1 nM to 10 μM for 24-72 hours. Cell viability is assessed using MTT or CCK-8 assays to determine IC₅₀ values. Cell cycle analysis is performed by flow cytometry using propidium iodide staining to assess mitotic arrest. Apoptosis is assessed using Annexin V/PI staining and caspase activity assays.
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| Animal Protocol |
In vivo animal studies for docetaxal are typically conducted in xenograft mouse models using human cancer cell lines. Tumor-bearing mice are treated with the compound via intravenous injection, the standard route of administration for taxanes. Tumor volume is measured over time to assess efficacy. Body weight and clinical signs are monitored to assess tolerability. Tissue samples are collected for histopathological analysis and biomarker evaluation. Standard pharmacokinetic parameters are determined from plasma samples.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for docetaxal are limited in the published literature. As a docetaxel analog with molecular weight 849.92 g/mol, the compound is expected to have pharmacokinetic properties similar to docetaxel. Taxanes are typically administered intravenously due to poor oral bioavailability. The compounds are highly protein-bound and extensively metabolized by CYP3A4. The 10-acetyl modification may affect the compound's metabolic stability and clearance compared to docetaxel.
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| Toxicity/Toxicokinetics |
Specific toxicity data for docetaxal are limited in the published literature. As a docetaxel analog, the compound is expected to have a toxicity profile similar to docetaxel, which includes myelosuppression, neuropathy, fluid retention, and hypersensitivity reactions. Taxanes are known to have significant dose-limiting toxicities. The compound is intended for research use only and is not approved for clinical use as a distinct entity.
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| References |
[1]. Gueritte-Voegelein, et al. Relationships between the structure of taxol analogs and their antimitotic activity. Journal of Medicinal Chemistry, J Med Chem. 1991 Mar;34(3):992-8.
[2]. Yao, Peng, et al. Preparation of crystal form of dihydrate and DMSO solvate of anticancer compound CX1409. CN107793382A. [3]. X‑ray Crystal Structure-Guided Discovery of Novel Indole Analogues as Colchicine-Binding Site Tubulin Inhibitors with Immune- Potentiating and Antitumor Effects against Melanoma. J Med Chem . 2023 May 25;66(10):6697-6714. |
| Additional Infomation |
Docetaxal (10-Acetyl docetaxel, PNU-101383) is an analog of the chemotherapeutic agent docetaxel, functioning as a microtubule disassembly inhibitor with anticancer activity. It has molecular formula C₄₅H₅₅NO₁₅ and molecular weight 849.92 g/mol. As an ADC payload compound, it may have applications in antibody-drug conjugate development. The compound is not approved for clinical use; all applications remain at the preclinical research stage.
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| Molecular Formula |
C45H55NO15
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|---|---|
| Molecular Weight |
849.92
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| Exact Mass |
849.357
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| CAS # |
125354-16-7
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| PubChem CID |
147895
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
901.4±65.0 °C at 760 mmHg
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| Flash Point |
499.0±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.606
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| LogP |
7.19
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
61
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| Complexity |
1770
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| Defined Atom Stereocenter Count |
11
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| SMILES |
CC1=C2[C@H](C(=O)[C@@]3([C@H](C[C@@H]4[C@]([C@H]3[C@@H]([C@@](C2(C)C)(C[C@@H]1OC(=O)[C@@H]([C@H](C5=CC=CC=C5)NC(=O)OC(C)(C)C)O)O)OC(=O)C6=CC=CC=C6)(CO4)OC(=O)C)O)C)OC(=O)C
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| InChi Key |
LEMYAXKYCOBYOJ-OAGWZNDDSA-N
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| InChi Code |
InChI=1S/C45H55NO15/c1-23-28(58-39(53)33(50)32(26-16-12-10-13-17-26)46-40(54)61-41(4,5)6)21-45(55)37(59-38(52)27-18-14-11-15-19-27)35-43(9,29(49)20-30-44(35,22-56-30)60-25(3)48)36(51)34(57-24(2)47)31(23)42(45,7)8/h10-19,28-30,32-35,37,49-50,55H,20-22H2,1-9H3,(H,46,54)/t28-,29-,30+,32-,33+,34+,35-,37-,43+,44-,45+/m0/s1
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| Chemical Name |
[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-1,9-dihydroxy-15-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]oxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
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| Synonyms |
Docetaxal; 125354-16-7; 10-Acetyl Docetaxel; N-Debenzoyl-N-(tert-butoxycarbonyl)taxol; [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-1,9-dihydroxy-15-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]oxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate; Benzenepropanoic acid, beta-[[(1,1-dimethylethoxy)carbonyl]amino]-alpha-hydroxy-, (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester, (alphaR,betaS)-; 10-Acetyltaxotere; 10-Acetyldocetaxel;
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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: 100 mg/mL (117.66 mM)
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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 | 1.1766 mL | 5.8829 mL | 11.7658 mL | |
| 5 mM | 0.2353 mL | 1.1766 mL | 2.3532 mL | |
| 10 mM | 0.1177 mL | 0.5883 mL | 1.1766 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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