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.    

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Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Docetaxel (CAS No.: 114977-28-5) is an important antitumor drug, belonging to the semi-synthetic yew compounds, originally derived from paclitaxel. As a microtubule unpolymerization inhibitor, docetaxel stabilizes microtubule structures, blocks the G2/M phase of the cell cycle, induces tumor cell apoptosis, and demonstrates significant anticancer activity. Since the late 1990s, docetaxel has been widely used in clinical treatment of various solid tumors, especially showing good efficacy in breast cancer, non-small cell lung cancer, and prostate cancer. This article will systematically review the chemical structure, origin, pharmacological activity, mechanism of action, druggability, and current clinical application status of docetaxel, aiming to provide comprehensive reference materials for researchers in the field of natural product pharmacology.

Chemical structure and physicochemical properties

Docetaxel has the molecular formula C43H53NO14 and a molecular weight of 807.89, making it a semi-synthetic derivative of taxane diterpene compounds. Its chemical structure is based on the core backbone of paclitaxel, distinguished by side chain modification, giving it superior pharmacological performance and pharmacokinetic characteristics. The LogP value of docetaxel is about 3.071, indicating moderate lipophilicity, which facilitates cell membrane penetration. Its polar surface area (TPSA) is 224.45 Ų, indicating that its molecules have a high number of polar groups, which affects their water solubility and bioavailability. Docetaxel has low water solubility (about 0.0096 mg/mL), which limits its solubility in the aqueous phase, and usually requires excipients such as polyethylene glycol or ethanol for formulation optimization. The low permeability of the blood-brain barrier suggests its limited distribution in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test result was 0.0, indicating a low genotoxicity risk.

Plant Origins and Extraction Methods

The parent compound of docetaxel, paclitaxel, originally comes from the bark of Pacific yew (Taxus brevifolia), but natural paclitaxel yields are extremely low and extraction is complex. docetaxel is obtained by semi-synthesizing paclitaxel, mainly using 10-deacetylbaccatin III extracted from cell cultures or leaves of taxus species such as Taxus baccata, as the starting material, and synthesized through a series of chemical modifications. This method overcomes the yield limitations of direct extraction from natural products, improving production efficiency and purity. In recent years, with advances in plant cell culture technology and biosynthetic engineering, research on synthesizing docetaxel using plant cell fermentation and genetic engineering methods has gradually increased, making large-scale green production possible in the future.

Pharmacological activity research

As a microtubule depolymerization inhibitor, docetaxel significantly inhibits tumor cell proliferation. Its IC50 value is about 0.2 μM, indicating potent cytotoxicity. In vitro experiments have shown that docetaxel can effectively inhibit the growth of various tumor cell lines, including breast cancer, non-small cell lung cancer, ovarian cancer, and others. Its antitumor activity is not only reflected in inhibiting cell proliferation, but also in inducing cell cycle arrest and apoptosis. Docetaxel promotes activation of the cell apoptosis pathway by reducing the expression of anti-apoptotic genes bcl-2 and bcl-xL. Additionally, docetaxel has a certain inhibitory effect on tumor cell migration and invasion, possibly by regulating matrix metalloproteinases (MMPs) and other related molecules.

In animal models, docetaxel demonstrated good antitumor effects, significantly extending survival in tumor-bearing animals. Its combination chemotherapy regimen has become one of the standard treatments for various cancers, demonstrating potential for synergistic effects and resistance reversal.

Mechanism of action and molecular targets

The main mechanism of action of docetaxel is to bind to microtubule proteins, stabilize microtubule structures, inhibit the deaggregation process, and lead to cytoskeletal dysfunction. The stability of microtubules blocks the progression of the G2/M phase of the cell cycle, preventing normal cell division and ultimately triggering the apoptotic signaling pathway.

At the molecular level, docetaxel affects several key targets:

• AMPK (PRKAA1): docetaxel can activate the energy-sensing kinase AMPK, regulate cellular metabolism and survival signals, and promote metabolic stress and death in tumor cells.
• BCL2 (BCL2): As an anti-apoptotic protein, its expression is downregulated by docetaxel, reducing the cell's ability to resist apoptosis.
• STAT3: docetaxel inhibits the STAT3 signaling pathway, blocking tumor cell proliferation and immune escape.
• ESR2 (ESR2): Regulation of estrogen receptor β may affect the sensitivity of breast cancer cells to docetaxel.
• ABCB1 (P-gp) and ABCG2: docetaxel is the substrate of these two ATP-binding cassette transporters, affecting drug efflux and resistance.
• PRKCA (protein kinase Cα): involved in regulating cell proliferation and apoptosis signals.
• MAPT (microtubule-associated protein Tau): affects microtubule stability and may regulate the efficacy of docetaxel.
• MMP2 (matrix metalloproteinase 2): docetaxel inhibits MMP2 expression, reducing tumor cell invasion and metastatic ability.
• LCK (lymphocyte-specific tyrosine kinase): may be involved in regulating immune cell responses to tumors.

In summary, docetaxel achieves potent antitumor activity through multi-target and multi-pathway synergistic effects.

Druggability evaluation and pharmacokinetics

The physicochemical properties of docetaxel indicate moderate lipid solubility and high polar surface area, resulting in low water solubility and requiring special formulation techniques to improve bioavailability. Its low blood-brain barrier permeability limits its therapeutic application for central nervous system tumors.

Pharmacokinetic studies show that docetaxel is widely distributed in the body, mainly metabolized by the liver, with cytochrome P450 3A4 (CYP3A4) as the primary metabolic enzyme. The drug has a moderate half-life and is suitable for intermittent dosing. Its excretion mainly occurs through bile and is excreted through the intestines. Doxetaxel has many drug interactions, especially when used in combination with CYP3A4 inhibitors or inducers, requiring careful dose adjustment.

In terms of safety, docetaxel does not show significant hERG channel suppression and carries a low risk of cardiotoxicity. The Ames test was negative, indicating a low risk of genotoxicity. Common adverse reactions include bone marrow suppression, peripheral neuropathy, and fluid retention, which require close monitoring in clinical practice.

Prospects and outlooks for clinical applications

As a first- or second-line chemotherapy drug, docetaxel has been widely used in the treatment of various solid tumors such as breast cancer, non-small cell lung cancer, prostate cancer, and gastric cancer. By combining chemotherapy regimens with other drugs, it significantly improves treatment efficacy and patient survival rates. With the development of molecular targeted therapy and immunotherapy, docetaxel has become increasingly important in combination drug therapy.

Future research directions include:

• Overcoming resistance mechanisms: Developing resistance reversals for docetaxel targeting drug efflux mediated by ABCB1 and ABCG2.
• Targeted delivery systems: Using nanotechnology and targeted vectors to enhance docetaxel's tumor selectivity and bioavailability, reducing systemic toxicity.
• Combined immunotherapy: Exploring the combined use of docetaxel with immune checkpoint inhibitors to enhance anti-tumor immune responses.
• Personalized treatment strategy: Based on tumor molecular markers and patient genotype, optimize docetaxel dosage and dosing regimens to achieve precise treatment.

Moreover, advances in green synthesis and bioengineering technologies will drive the sustainable production of docetaxel, reduce costs, and expand clinical applications.

Conclusion

As a representative of taxane anti-tumor drugs, docetaxel has become an important clinical drug for tumor treatment thanks to its unique microtubule stabilization mechanism and multi-target effects. Its semi-synthetic source overcomes the limitations of extracting natural products, and its physicochemical properties and pharmacokinetic characteristics provide strong support for its clinical application. In the future, with deeper analysis of molecular mechanisms and the application of new technologies, docetaxel is expected to play a greater role in cancer treatment, driving the continued development of natural product pharmacology and cancer treatment.