Synonym name:
Catalogue No.: BP0514
Cas No.: 114977-28-5
Formula: C43H53NO14
Mol Weight: 807.89
Botanical Source:
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams, up to kgs.
GMP is availale on request.
Inquire for bulk scale.
Description:
Docetaxel is an antineoplastic drug by inhibiting microtubule depolymerization, and attenuating of the effects of bcl-2 and bcl-xL gene expression.
References:
Cancer Treat Rev. 2015 Mar;41(3):262-70.
Balancing activity and tolerability of neoadjuvant paclitaxel- and docetaxel-based chemotherapy for HER2-positive early stage breast cancer: sensitivity analysis of randomized trials.
Paclitaxel and Docetaxel represent the most adopted taxanes in the neoadjuvant treatment of HER2-positive breast cancer. Questions still remain with regard to their difference in terms of activity and tolerability.
METHODS AND RESULTS:
Events for pathological complete response (pCR), severe and febrile neutropenia (FN), and severe neurotoxicity were pooled by adopting a fixed- and random-effect model. A sensitivity analysis to test for the interaction between paclitaxel and Docetaxel was accomplished. Absolute differences with 95% confidence intervals (CIs) and the number of patients needed to treat/harm (NNT/NNH) were calculated to derive the Likelihood of being Helped or Harmed (LHH). Data from 15 trials (3601 patients) were included. Paclitaxel significantly increases pCR rate by 6.8% in comparison with Docetaxel (43.4%, 95% CI 41.1-45.7% versus 36.6%, 95% CI 34.3-39.0%, p=0.0001), regardless of the chemotherapy backbone, with an absolute difference of 9% and 9.2% for anthracycline-based or free-regimens. Paclitaxel significantly improves pCR versus Docetaxel with a single HER2-inhibition by 6.7% (p=0.0012), with no difference if combined with a dual HER2-inhibition. Severe neutropenia and FN are significantly lower with paclitaxel, with an absolute difference of 32.4% (p<0.0001) and 2.5% (p=0.0059), respectively. Conversely, severe neurotoxicity is slightly higher with paclitaxel (3%, p=0.0001). The LHH ratio calculated for pCR and severe neutropenia is 2.0 and 0.7 for paclitaxel and Docetaxel.
CONCLUSIONS:
Although the activity of neoadjuvant paclitaxel and Docetaxel HER2-positive breast cancer is considered similar, the slight advantage in pCR, the significantly lower neutropenia and FN, do favor paclitaxel (in the weekly fashion) over Docetaxel, despite the slightly worst neurotoxicity.
BJU Int. 2015 May;115(5):744-52.
Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer.
To evaluate the benefit of Docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line Docetaxel.
METHODS AND RESULTS:
We retrospectively reviewed the records of consecutive patients with mCRPC with a good response to first-line Docetaxel [serum prostate specific antigen (PSA) decrease ≥50%; no clinical/radiological progression]. We analysed the impact of management at relapse (Docetaxel rechallenge or non-taxane-based therapy) on PSA response, symptomatic response (performance status/pain/analgesic consumption), and overall survival (OS). We used multivariate stepwise logistic regression to analyse potential predictors of a favourable outcome. We identified 270 good responders to first-line Docetaxel. The median progression-free interval (PFI) was 6 months from the last Docetaxel dose. At relapse, 223 patients were rechallenged with Docetaxel (82.5%) and 47 received non-taxane-based therapy. There was no significant difference in median OS {18.2 [95% confidence interval (CI) 16.1-22.00] and 16.8 [95%CI 13.4-21.5] months, respectively, P = 0.35}. However, good PSA response and symptom relief/stable disease were more frequent on Docetaxel rechallenge (40.4% vs 10.6%, P < 0.001 for PSA). A PFI of >6 months and added estramustine predicted a good PSA response and symptomatic response on Docetaxel rechallenge but only a PFI of >6 months predicted longer OS. Haemoglobin (<13 g/dL) and pain were associated with reduced OS. Docetaxel rechallenge increased the incidence of grade ≥3 sensory neuropathy, nail disorders and asthenia/fatigue.
CONCLUSIONS:
Docetaxel rechallenge is a management option for responders to Docetaxel with a PFI of >6 months, but did not prolong survival. Potential benefits should be weighed against the risk of cumulative toxicity.
N Engl J Med. 2004 Oct 7;351(15):1513-20.
Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer.
Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer.
METHODS AND RESULTS:
We compared Docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormone-independent prostate cancer. Of 674 eligible patients, 338 were assigned to receive Docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given Docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given Docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving Docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups.
CONCLUSIONS:
The improvement in median survival of nearly two months with Docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Docetaxel (CAS number: 114977-28-5) is an important anti-tumor drug, belonging to the taxane class of semi synthetic compounds, originally derived from paclitaxel. As a microtubule depolymerization inhibitor, docetaxel exhibits significant anti-cancer activity by stabilizing microtubule structures, blocking the G2/M phase of the cell cycle, inducing tumor cell apoptosis. Since the late 1990s, docetaxel has been widely used in the clinical treatment of various solid tumors, especially in the fields of breast cancer, non-small cell lung cancer, prostate cancer, etc. This article provides a systematic review of the chemical structure, sources, pharmacological activities, mechanisms of action, drug properties, and clinical applications of docetaxel, aiming to provide comprehensive reference materials for researchers in the field of natural product pharmacology.
The molecular formula of docetaxel is C43H53NO14, with a molecular weight of 807.89, and it belongs to the semi synthetic derivatives of taxane diterpenes. Its chemical structure is based on the core skeleton of paclitaxel, with the difference being the modification of side chains, which gives it superior pharmacological properties and pharmacokinetic characteristics. The LogP value of docetaxel is approximately 3.071, indicating its moderate lipid solubility, which is beneficial for membrane penetration. Its polar surface area (TPSA) is 224.45 Å ², indicating that its molecules have a large number of polar groups, which affect its water solubility and bioavailability. Docetaxel has low water solubility (approximately 0.0096 mg/mL), which limits its solubility in aqueous phase. Therefore, it is usually necessary to optimize the formulation with excipients such as polyethylene glycol or ethanol. The low permeability of the blood-brain barrier suggests its limited distribution in the central nervous system. The negative result of hERG channel inhibition experiment indicates a low risk of cardiac toxicity. The Ames mutagenicity test result is 0.0, indicating a low risk of genetic toxicity.
The parent compound of docetaxel, paclitaxel, was originally derived from the bark of Pacific yew (Taxus brevifolia), but the production of natural paclitaxel is extremely low and the extraction process is complex. Docetaxel is obtained through a semi synthetic method of paclitaxel, mainly using 10 deacetylbaccatin III extracted from cell culture or leaves of taxus baccata and other taxus plants as the starting material, and synthesized through a series of chemical modifications. This method overcomes the yield limitation of direct extraction of natural products, improving production efficiency and purity. In recent years, with the advancement of plant cell culture technology and biosynthetic engineering, research on the synthesis of docetaxel using plant cell fermentation and genetic engineering methods has gradually increased, providing possibilities for large-scale green production in the future.
Docetaxel, as a microtubule depolymerization inhibitor, significantly inhibits the proliferation of tumor cells. Its IC50 value is approximately 0.2 μ M, indicating potent cytotoxicity. In vitro experiments show that docetaxel can effectively inhibit the growth of many tumor cell lines, including breast cancer, non-small cell lung cancer, ovarian cancer, etc. Its anti-tumor activity is not only reflected in cell proliferation inhibition, but also in inducing cell cycle arrest and apoptosis. Docetaxel promotes the activation of cell apoptosis pathways by reducing the expression of anti apoptotic genes Bcl-2 and Bcl xL. In addition, docetaxel also has a certain inhibitory effect on the migration and invasion of tumor cells, which may be achieved by regulating related molecules such as matrix metalloproteinases (MMPs).
In animal models, docetaxel exhibits good anti-tumor effects and significantly prolongs the survival of animals with tumor burden. The combination chemotherapy regimen has become one of the standard treatments for various cancers, demonstrating the potential for synergistic enhancement and resistance reversal.
The main mechanism of action of docetaxel is to bind to microtubule proteins, stabilize microtubule structure, inhibit microtubule depolymerization process, and lead to dysfunction of the cytoskeleton. The stability of microtubules blocks the G2/M phase progression of the cell cycle, preventing normal cell division and ultimately triggering the apoptotic signaling pathway.
At the molecular level, docetaxel affects multiple key targets:
In summary, docetaxel achieves its potent anti-tumor activity through multi-target and multi pathway synergistic effects.
The physicochemical properties of docetaxel show moderate lipid solubility and high polar surface area, resulting in low water solubility, requiring special formulation techniques to improve bioavailability. Its low blood-brain barrier permeability limits the therapeutic application of central nervous system tumors.
Pharmacokinetic studies have shown that docetaxel is widely distributed in the body, mainly metabolized through the liver, and the metabolic enzyme is mainly cytochrome P450 3A4 (CYP3A4). The drug has a moderate half-life and is suitable for intermittent administration. Its excretion is mainly through bile, which is excreted through the intestine. Docetaxel has many drug interactions, especially when used in combination with CYP3A4 inhibitors or inducers, dosage adjustment should be cautious.
In terms of safety, docetaxel does not exhibit significant hERG channel inhibition and has a low risk of cardiac toxicity. Ames test negative, low risk of genetic toxicity. Common adverse reactions include bone marrow suppression, peripheral neuropathy, fluid retention, etc., which should be closely monitored in clinical application.
As a first-line or second-line chemotherapy drug, docetaxel has been widely used in the treatment of breast cancer, non-small cell lung cancer, prostate cancer, gastric cancer and other solid tumors. It significantly improves treatment efficacy and patient survival rate by synergizing with other drugs through a combination chemotherapy regimen. With the development of molecular targeted therapy and immunotherapy, the position of docetaxel in combination therapy has become increasingly important.
Future research directions include:
In addition, the development of green synthesis and biotechnology will promote the sustainable production of docetaxel, reduce costs, and expand the scope of clinical applications.
Docetaxel, as a representative of paclitaxel based anti-tumor drugs, has become an important drug for clinical cancer treatment due to its unique microtubule stabilization mechanism and multi-target effects. Its semi synthetic source overcomes the limitations of natural product extraction, and its physicochemical properties and pharmacokinetic characteristics provide strong support for its clinical application. In the future, with the in-depth analysis of molecular mechanisms and the application of new technologies, docetaxel is expected to play a greater role in the field of anti-cancer therapy, promoting the continuous development of natural product pharmacology and tumor therapy.
