Docetaxel

SKU: orb1309994

Description

Docetaxel is a semi-synthetic taxane that stabilizes microtubules, inhibiting their depolymerization with an IC50 of 0.2 µM. It promotes apoptosis by downregulating bcl-2 and bcl-xL, demonstrating potent anti-tumor activity in both cellular assays and animal models for cancer research.

Research Area

Cell Biology, Metabolism Research, Signal Transduction

Key Properties

• CAS Number: 114977-28-5
• MW: 807.88
• Purity: 99.29% (May vary between batches)
• Formula: C₄₃H₅₃NO₁₄
• SMILES: O(C(C)=O)[C@]12[C@]3([C@H](OC(=O)C4=CC=CC=C4)[C@@]5(O)C(C)(C)C([C@@H](O)C(=O)[C@]3(C)[C@@H](O)C[C@]1(OC2)[H])=C(C)[C@@H](OC([C@@H]([C@@H](NC(OC(C)(C)C)=O)C6=CC=CC=C6)O)=O)C5)[H]
• Target: Microtubule Associated,Apoptosis,Endogenous Metabolite
• Solubility: Ethanol:80.8 mg/mL (100.01 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:8.08 mg/mL (10 mM);DMSO:257 mg/mL (318.12 mM)

Bioactivity

• Target IC50:
  Microtubule:0.2 μM|PC3 cells:3.08 ± 0.4 nM|NCI-H4 cells (24 h):116 nM|NCI-H4 cells60 cells (72 h):30 nM|NCI-60 cells:14-34 nM|LNCaP cells:1.46 ± 0.2 nM
• In Vivo:
  METHODS: To detect anti-tumor activity in vivo, Docetaxel (5-10 mg/kg) and PD-1 inhibitor (200 μg/only) were intraperitoneally injected into CB17 SCID mice carrying mouse prostate cancer tumor RM-1 five times a week for ten days. RESULTS: PD-1 inhibitor combined with Docetaxel had a synergistic effect on prostate cancer in mice, inhibiting the growth of prostate tumors, increasing the survival rate and reducing adverse effects. METHODS: To assay antitumor activity in vivo, Docetaxel (7.5-15 mg/kg, intratumorally injected IT twice weekly for six weeks; or 20-40 mg/kg weekly intravenously injected IV) was administered to C57BL/6 mice harboring HNSCC tumors HN30 or HN12. RESULTS: IT Docetaxel improved overall survival and disease-free survival and reversed tumor growth. At equivalent dose levels, IT Docetaxel resulted in 26-fold higher peak tumor concentrations and 24-fold longer tumor exposure than IV treatment.
• In Vitro:
  METHODS: Human lung cancer cells NCI-H460 were treated with Docetaxel (0.2-200 nmol/L) for 24-72 h, and cell viability was measured by MTS. RESULTS: The IC50 of NCI-H460 to Docetaxel was 0.030 μmol/L at 72 h and 0.116 μmol/L at 24 h. METHODS: Human prostate cancer cells PC-3, DU-145 and LNCaP were treated with Docetaxel (0.5-4 nM) for 48 h. Apoptosis was detected by Flow Cytometry. RESULTS: High-dose Docetaxel treatment significantly increased the proportion of Annexin V+ apoptotic cells.
• Cell Research:
  NCI-H460 cells (4 × 10^3) were grown in 100 μl of DMEM medium containing serum per well in a 96-well plate. After 24 h, the cells were treated with docetaxel (0, 0.2, 0.63, 2, 6.3, 20, 63 and 200 nmol/L, respectively) for 72 h. Every treatment was triplicate in the same experiment. Then 20 μl of MTS was added to each well for 1 to 4 h at 37°C. After incubation, the absorbance was read at a wavelength of 490 nm according to the manufacturer's protocol. The IC50 calculation was performed with GraphPad Prism 5.0 software .
• Animal Research:
  Docetaxel (0, 10, 20, 30, 40, 60, and 80 mg/kg per week) was given once a week for 3 weeks for mice. Because more than 30 mg/kg per week of the drug caused body weight loss in mice, 20 mg/kg per week of docetaxel was judged to be the maximum nontoxic dose. Docetaxel (20 mg/kg per week) was given to mice once a week for 3 weeks at one of the following different points (2, 10, 14, or 22 HALO). Seventy-two hours after the final dosing of the agent, the intestinal mucosa of the small intestine (proximal 8 cm) was removed, fixed in 20 N Mildform solution (containing 8% formaldehyde in a buffered solution), and embedded in paraffin blocks, and sections of 5 mm were put on glass slides. Apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method, using the Apop Tag Peroxidase In Situ Apoptosis Detection Kit. Specimens were dewaxed and immersed in phosphate-buffered saline for 5 minutes at room temperature, incubated with 20 mg/ml proteinase K for 15 minutes at room temperature, and then quenched of endogenous peroxidase in 2% hydrogen peroxide in phosphate-buffered saline. Terminal deoxynucleotidyl transferase enzyme was applied directly onto the specimens, which were then incubated at 37°C for 1 hour. The reaction was terminated by transferring the slides to stop/wash buffer for 10 minutes at room temperature, and then specimens were covered with peroxidase-conjugated anti-digoxigenin antibody and incubated for 30 minutes at room temperature. Specimens were then soaked in staining buffer containing 0.05% diaminobenzidine to achieve color development. Finally, the specimens were counterstained by immersion in Mayer's hematoxylin solution. Apoptotic cells were counted under a light microscope in a good longitudinal crypt section. Starting at the base of the crypt column, the TUNEL-positive cells were counted up to the 18th cell position in each crypt.One hundred crypt sections were scored in each animal, and a frequency of TUNELpositive cells per crypt was calculated. Dosing time-dependent influence of docetaxel on intestinal apoptosis was also examined in female Balb/c mice .

Storage & Handling

• Storage: keep away from direct sunlight,keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RP 56976, RP56976, RP-56976, Docetaxel, Apoptosis, EndogenousMetabolite, Endogenous Metabolite, Inhibitor, MicrotubuleAssociated, Microtubule Associated, Microtubule/Tubulin, microtubule, NSC 628503, NSC628503, NSC-628503, inhibit

Compound Identifiers

PubChem CID

148124

Silvia Breusa a b , Eloise Thomas a , Noemi Baldinotti a , Serena Zilio a 1 , Jean-Guy Delcros c , Diana Marcela Hernandez-Palomino d , Weisha Qi e , Hanäé Guérin a , Benjamin Gibert b f , Patrick Mehlen b g , Ilaria Marigo d e , David Kryza a h , Giovanna Lollo Anti-Netrin-1 decorated nanoparticles combined with chemotherapy for the treatment of triple-negative breast cancer Biomaterials Advances, (2024)

PubMed: