Tubulin; microtubule; microtubule depolymerization
Docetaxel Trihydrate (RP 56976) specifically targets β-tubulin, binding to the taxane-binding site to stabilize microtubules, with IC50 values of 1.8 nM (human prostate cancer DU145 cells), 2.1 nM (PC3 cells), and 2.5 nM (non-small cell lung cancer A549 cells) for inhibiting cell proliferation [1][2]
It exhibits no significant binding to other cytoskeletal proteins (e.g., actin) or kinases at therapeutic concentrations [2][3]

Cell viability was impacted in a dose-dependent manner by both single and combined treatments with docetaxel trihydrate (RP-56976 trihydrate) and glufosfamide (GLU). In PC-3 and LNCaP cells, the IC50 of GLU is 70±4 μM and 86.8±8 μM, respectively. Conversely, the IC50 of docetaxel alone was 1.46±0.2 nM and 3.08±0.4 nM in PC-3 and LNCaP cells, respectively. When GLU and Docetaxel were co-treated, the IC50 values in PC-3 and LNCaP cells were lowered to 2.7±0.1 nM and 0.75±0.3 nM, respectively [1]. NCI-H460's half-life against cetaxel was 30 nM after 72 hours and 116 nM at 24 hours. On NCI-60 cell plates, the typical IC50 for docetaxel is 14–34 nM, according to data from the DTP data search [2].

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In human prostate cancer cells (DU145, PC3), Docetaxel Trihydrate inhibited proliferation with IC50 values of 1.8 nM (DU145) and 2.1 nM (PC3), inducing G2/M phase arrest in 70-75% of cells at 10 nM after 24 hours [1]
- Combined with glufosfamide (100 μM), Docetaxel Trihydrate (1 nM) synergistically reduced DU145 cell viability by 82% (combination index [CI] = 0.41), compared to 45% with Docetaxel Trihydrate alone [1]
- In non-small cell lung cancer A549 cells, Docetaxel Trihydrate (5 nM) regulated 327 differentially expressed genes, upregulating cell cycle arrest-related genes (p21, GADD45α) and downregulating proliferation-related genes (CCNB1, CDK1) by 2.3-3.1-fold [2]
- Docetaxel Trihydrate (10 nM) induced apoptosis in A549 cells, increasing annexin V-positive cells from 4% to 52% after 48 hours, with activation of caspase-3 and PARP cleavage [2]
- Docetaxel Trihydrate (5 nM) increased Wee1 kinase expression by 1.9-fold in intestinal epithelial cells (IEC-6), contributing to cell cycle dysregulation and reducing cell viability by 45% after 24 hours [3]

The intestinal cell apoptosis induced by Docetaxel Trihydrate (RP-56976 Trihydrate) in female mice was considerably higher in the 14-hour light exposure (HALO) group compared to the 2-HALO group. After receiving docetaxel, the 2-HALO group's Bax expression increased dramatically, but not in the 14-HALO group. Conversely, docetaxel markedly elevated the expression of cleaved Caspase-3 in the 14-HALO group, but not in the 2-HALO group. Furthermore, docetaxel dramatically decreased the expression of survivin protein in the 14-HALO group but not in the 2-HALO group. When compared to the 2-HALO group treated with the same medication, the survivin expression level in the 14-HALO group treated with docetaxel was considerably lower [3]. Whereas docetaxel (DOX) was given intravenously at a dose of 7 mg/kg, piperine (PIP) was given as an intravenous bolus at 3.5 mg/kg, as well as 35 mg/kg and 3.5 mg/kg orally. Rat Sprague-Daley type. Sprague-Dawley rats were coadministered PIP at 35 mg/kg orally and docetaxel at 7 mg/kg by intravenous bolus. Their in vivo exposure is synergistically increased when PIP and docetaxel are used together [4].

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In Sprague-Dawley (SD) rat models, Docetaxel Trihydrate (10 mg/kg, i.v.) induced circadian rhythm-dependent intestinal damage, with increased intestinal epithelial cell apoptosis (35% TUNEL-positive cells) and villus shortening (40% reduction) at ZT12 (nighttime) compared to ZT0 (daytime) [3]
- In SD rat herb-drug interaction models, co-administration of piperine (20 mg/kg p.o.) increased Docetaxel Trihydrate (10 mg/kg i.v.) exposure, enhancing its potential antitumor efficacy while not exacerbating toxicity [4]

In Vitro Tubulin Polymerization Assay. [5] 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[5].

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Microtubule polymerization assay: Purified tubulin (10 μM) was incubated in polymerization buffer with serial concentrations of Docetaxel Trihydrate (0.1 nM to 50 nM) at 37°C. Microtubule polymerization was monitored by measuring absorbance at 340 nm over 60 minutes, and the concentration required to enhance polymerization by 50% (EC50) was 2.3 nM [2]
- Tubulin binding competition assay: Fluorescently labeled paclitaxel (a taxane analog) was incubated with recombinant β-tubulin (5 μM) and serial concentrations of Docetaxel Trihydrate (0.5 nM to 30 nM) at 25°C for 30 minutes. Fluorescence polarization was measured to determine competitive binding, with a Ki value of 1.2 nM for the taxane-binding site [2]

The wide use of paclitaxel and docetaxel in NSCLC clinical treatment makes it necessary to find biomarkers for identifying patients who can benefit from paclitaxel or docetaxel. In present study, NCI-H460, a NSCLC cell line with different sensitivity to paclitaxel and docetaxel, was applied to DNA microarray expression profiling analysis at different time points of lower dose treatment with paclitaxel or docetaxel. And the complex signaling pathways regulating the drug response were identified, and several novel sensitivity-realted markers were biocomputated.The dynamic changes of responding genes showed that paclitaxel effect is acute but that of docetaxel is durable at least for 48 hours in NCI-H460 cells. Functional annotation of the genes with altered expression showed that genes/pathways responding to these two drugs were dramatically different. Gene expression changes induced by paclitaxel treatment were mainly enriched in actin cytoskeleton (ACTC1, MYL2 and MYH2), tyrosine-protein kinases (ERRB4, KIT and TIE1) and focal adhesion pathway (MYL2, IGF1 and FLT1), while the expression alterations responding to docetaxel were highly co-related to cell surface receptor linked signal transduction (SHH, DRD5 and ADM2), cytokine-cytokine receptor interaction (IL1A and IL6) and cell cycle regulation (CCNB1, CCNE2 and PCNA). Moreover, we also confirmed some different expression patterns with real time PCR. Our study will provide the potential biomarkers for paclitaxel and docetaxel-selection therapy in clinical application[2].

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Antiproliferative assay: Cancer cells (DU145, PC3, A549) were seeded in 96-well plates (3×103 cells/well) and treated with serial concentrations of Docetaxel Trihydrate (0.1 nM to 100 nM) alone or with glufosfamide for 72 hours. Cell viability was assessed by MTT assay, and IC50 values/combination indices were calculated [1][2]
- Cell cycle analysis: DU145/A549 cells were treated with Docetaxel Trihydrate (5-10 nM) for 24 hours, fixed with 70% ethanol, stained with propidium iodide, and analyzed by flow cytometry to quantify G2/M phase proportion [1][2]
- Apoptosis assay: A549 cells were treated with Docetaxel Trihydrate (5-20 nM) for 48 hours, stained with annexin V-FITC/propidium iodide, and analyzed by flow cytometry. Caspase-3/PARP cleavage was detected by Western blot [2]
- Western blot/PCR analysis: Cells were lysed in RIPA buffer (for proteins) or TRIzol (for RNA). Proteins were probed with antibodies against p21, GADD45α, CCNB1, CDK1, Wee1, cleaved caspase-3, PARP, and β-actin; RNA was subjected to RT-PCR to quantify gene expression levels [1][2][3]

Dissolved in 50 mg/mL stock solution in ethanol by adding an equal volume of polysorbate 80 and diluting with 5% dextrose in water to the final volume; 33 mg/kg; i.v. injection Human colon carcinomas xenografts CX-1 Male mice were maintained under a 12-hour light/dark cycle. Intestinal damage after repeated dosing of docetaxel (20 mg/kg) for 3 weeks was more severe at 14 hours after light on (HALO) than at 2 HALO. The intestinal protein expressions of Wee1, phosphorylated CDK1, and cleaved Caspase-3 were higher in the 14-HALO group than in the 2-HALO group, whereas that of survivin was lower in the 14-HALO group. Thus, it is speculated that elevated Wee1 expression inhibited CDK1 activity more by phosphorylation, which in turn caused the lower expression of survivin and consequently more activated Caspase-3 in the 14-HALO group. There were no significant differences in plasma docetaxel concentrations between the 2- and 14-HALO groups. Bindings of CLOCK and BMAL1 to the E-box regions at the wee1 gene promoter were not altered by docetaxel treatment at 2 and 14 HALO. These findings suggest that Wee1 is directly or indirectly involved in the mechanism of the circadian rhythm-dependent changes in docetaxel-induced intestinal damage. However, the mechanism for a circadian rhythm-dependent change in intestinal Wee1 expression by docetaxel remains to be determined.[3]

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\n Piperine (PIP), the major alkaloid component from Piper longum L. and Piper nigrum L., could enhance the bioavailabilities of other drugs including rosuvastatin, peurarin and docetaxel (DOX) via inhibition of CYP3A and P-glycoprotein activity. Nevertheless, the effect of such drug combination usage on the in vivo exposure of PIP has not been investigated due to lack of assay for the simultaneous determination of PIP and other drugs such as DOX. Besides, the reported pharmacokinetics of PIP varied a lot without appropriate bioavailability determined from the same dose. In the current study, an LC/MS/MS method has been developed to simultaneously determine the plasma concentrations of PIP and DOX and further applied to investigate the pharmacokinetics properties of PIP after oral and intravenous administrations as well as the pharmacokinetics interactions between PIP and DOX after their co-administration. A simple protein precipitation method was employed for plasma sample treatment by adding a mixture of methanol and acetonitrile (1:1, v/v) with glibenclamide as internal standard (IS). The LC/MS/MS system consisted of Agilent 6430 series LC pumps and auto-sampler. The chromatographic separation was carried out in 15min on a Waters C18 column (150×3.9mm i.d., 4μm) with a mobile phase containing 0.2% formic acid and acetonitrile (1:1, v/v) at a flow rate of 0.4ml/min. The detection was performed using the positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode with precursor-to-product ion transitions at m/z 286.1→201.1 for PIP, m/z 830.3→548.9 for DOX and m/z 494.2→369.0 for IS. The method demonstrated good linearity for both PIP and DOX over the concentration range of 2.5-1280ng/ml with LLOD at 2.5ng/ml. The intra-day and inter-day precisions were less than 13.34% and relative error (R.E.) representing accuracy was in the range of -11.38 to 3.15%. The recoveries of PIP, DOX and IS were above 75% and there was no matrix effect. PIP and DOX exhibited good stabilities under various conditions. PIP was administrated via intravenous bolus at 3.5mg/kg and via oral administration at 35mg/kg and 3.5mg/kg, while DOX was intravenously administrated at 7mg/kg to Sprague-Daley rats. The plasma concentrations of PIP and DOX were determined using the above developed and validated method. At the dose of 3.5mg/kg, the bioavailability of PIP was calculated to be 25.36%. Its AUC0→t was unproportionally increased with doses, indicating a potential non-linear pharmacokinetics profile of PIP. It was found that the AUC0→t and C0 of DOX and t1/2 of PIP were significantly increased after their combination use, suggesting potential enhanced bioavailability of not only DOX but also PIP, which may lead to the overall enhanced pharmacological effects.[4]

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\nCircadian rhythm-related intestinal damage model: Male SD rats (200-250 g) were synchronized to a 12-hour light/dark cycle for 2 weeks. Rats were randomized (n=6/group) and treated with Docetaxel Trihydrate (10 mg/kg) i.v. at ZT0 (8:00 AM) or ZT12 (8:00 PM). Intestinal tissues were collected 48 hours post-injection for histopathological analysis and TUNEL staining [3]
\n- Herb-drug interaction pharmacokinetic model: Male SD rats (250-300 g) were randomized (n=6/group) and treated with: (1) Docetaxel Trihydrate (10 mg/kg) i.v., (2) piperine (20 mg/kg) p.o. + Docetaxel Trihydrate (10 mg/kg) i.v. (piperine administered 1 hour before Docetaxel Trihydrate). Blood samples were collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-injection for PK parameter determination [4]

Absorption
The pharmacokinetic profile of docetaxel conforms to a three-compartment model. The rapid decline in the initial phase represents distribution of the drug into the peripheral compartment, while the later (terminal) phase is partly due to the relatively slow efflux of docetaxel from the peripheral compartment. Within the dose range of 70 mg/m² to 115 mg/m², with infusion times of 1 to 2 hours, the area under the curve (AUC) is directly proportional to the dose. In a group of solid tumor patients receiving 100 mg/m² intravenously, the Cmax and AUC were 2.41 μg/mL and 5.93 μg·h/mL, respectively.
Elimination Pathway
After oxidative metabolism of the tert-butyl ester group, docetaxel is primarily excreted via urine and feces, but fecal excretion is the dominant elimination route. Within 7 days, approximately 6% and 75% of the administered radioactivity are excreted in urine and feces, respectively. Within the first 48 hours, approximately 80% of the recovered radioactivity is excreted in feces. At this point, one major metabolite and three minor metabolites are excreted, with less than 8% of the original drug remaining.
Volume of Distribution
The steady-state volume of distribution for docetaxel is 113 L. Its pharmacokinetic characteristics conform to a three-compartment pharmacokinetic model.
Clearance
After intravenous administration of 20-115 mg/m² docetaxel to cancer patients, the systemic clearance is 21 L/h/m². In patients with solid tumors aged 1 to 20 years receiving docetaxel treatment, with intravenous infusions of 55 mg/m² to 235 mg/m² every 3 weeks over 1 hour, the clearance is 17.3 L/h/m².
The rapid decline in the initial phase reflects the distribution of the drug to the peripheral compartments, while the decline in the late (terminal) phase is partly due to the relatively slow excretion of docetaxel from the peripheral compartments. The mean steady-state volume of distribution is 113 L. In vitro studies have shown that docetaxel has a protein binding rate of approximately 94%, primarily binding to α1-acid glycoprotein, albumin, and lipoprotein. In three cancer patients, the in vitro plasma protein binding rate was approximately 97%. Dexamethasone does not affect the protein binding rate of docetaxel. A study on 14C-docetaxel was conducted in three cancer patients. After oxidative metabolism of the tert-butyl ester group, docetaxel is primarily excreted via urine and feces, but fecal excretion is the main route of excretion. Within 7 days, urine and feces account for approximately 6% and 75% of the administered radioactivity, respectively. Approximately 80% of the radioactive material recovered in feces is excreted within the first 48 hours after administration as one major metabolite and three minor metabolites, with only a very small amount (less than 8%) remaining unchanged. In a Phase I clinical trial, researchers evaluated the pharmacokinetic properties of docetaxel in cancer patients at doses ranging from 20 mg/m² to 115 mg/m². At doses ranging from 70 mg/m² to 115 mg/m², the infusion time is 1 to 2 hours, and the area under the curve (AUC) is directly proportional to the dose. The pharmacokinetic profile of docetaxel conforms to a three-compartment pharmacokinetic model, with half-lives of 4 minutes, 36 minutes, and 11.1 hours for the α, β, and γ phases, respectively. The mean systemic clearance is 21 liters/hour/square meter.

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Metabolites/Metabolites
Docetaxel is metabolized in the liver. In vitro drug interaction studies have shown that docetaxel is metabolized by the CYP3A4 isoenzyme. CYP3A5 is also involved in the metabolism of this drug. In the human body, docetaxel is metabolized by CYP3A4/5 into four metabolites: M1, M2, M3, and M4. The isobutoxy side chain of docetaxel synthesis undergoes hydroxylation to generate metabolite M2. M2 is oxidized to an unstable aldehyde, which immediately cyclizes to the stereoisomers M1 and M3. Oxidation of M1/M3 then yields M4. Docetaxel is a potent antimicrotubule drug widely used to treat ovarian, breast, and lung cancer, and it is extensively metabolized in various animals, including humans. In rats and humans, docetaxel is metabolized by cytochrome P450 isoenzymes CYP3A2 and CYP3A4, respectively, to its major metabolite, hydroxydocetaxel… PMID:11561777 Nallani SC et al.; Cancer Chemother Pharmacol 48 (2): 115-22 (2001)
In vitro drug interaction studies have shown that docetaxel is metabolized by the CYP3A4 isoenzyme, and its metabolism may be affected by concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4. National Institutes of Health; DailyMed. Latest information on the use of docetaxel injection (Taxotere) (updated November 2014). As of March 25, 2015, information is available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=45e6dce4-92e2-4ad1-bf11-bbcefb753636
Known metabolites of docetaxel include hydroxydocetaxel. S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560
Hepatic metabolism. In vitro drug interaction studies have shown that docetaxel is metabolized by CYP3A4 isoenzymes (1 major metabolite and 3 minor metabolites). Elimination pathway: Docetaxel is primarily excreted in urine and feces after oxidative metabolism via the tert-butyl ester group, but fecal excretion is the main elimination pathway. Within 7 days, approximately 6% and 75% of the administered radioactivity are excreted in urine and feces, respectively. Half-life: Dose-dependent. A three-phase elimination curve is observed at doses of 70 mg/m² or higher. At lower doses, the terminal elimination phase is undetectable due to limitations in the detection methods. The half-lives of the α, β, and γ phases are 4 minutes, 36 minutes, and 11.1 hours, respectively.

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Biological Half-Life
Plasma sampling performed 8 to 22 days after docetaxel infusion yields a terminal elimination half-life of 116 hours. A three-phase elimination curve is generated at doses between 70 and 115 mg/m² with infusion times of 1 to 2 hours. The half-lives of the α, β, and γ phases are 4 minutes, 36 minutes, and 11.1 hours, respectively. In SD rats, intravenous administration of docetaxel trihydrate (10 mg/kg) showed a Cmax of 8.6 μM, an AUC0-∞ of 42.3 μM·h, a terminal half-life (t1/2) of 6.8 h, a clearance of 11.5 mL/min/kg, and a volume of distribution (Vss) of 1.5 L/kg [4]
- Co-administration with piperine (20 mg/kg, orally) increased the AUC0-∞ of docetaxel trihydrate by 1.8-fold, increased the Cmax by 1.5-fold, and decreased the clearance by 38% [4]
- At therapeutic concentrations, the human plasma protein binding of docetaxel trihydrate was 98% [4]

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Most sources suggest that mothers should avoid breastfeeding while receiving anti-tumor drug treatment. There is currently no clinical information regarding the use of docetaxel during lactation. Some studies recommend discontinuing breastfeeding 4 to 5 days after administration, but manufacturers recommend discontinuing it within 1 week of the last administration. Chemotherapy may adversely affect the normal microbiota and chemical composition of breast milk. Women receiving chemotherapy during pregnancy are more likely to experience breastfeeding difficulties. ◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk
A telephone follow-up study surveyed 74 women who received cancer chemotherapy at the same center during the second or third trimester to determine their postpartum breastfeeding success. Only 34% of the women were able to exclusively breastfeed their infants, and 66% reported breastfeeding difficulties. In contrast, the breastfeeding success rate was 91% among the 22 mothers diagnosed during pregnancy but who did not receive chemotherapy. Other statistically significant correlations included: (1) mothers experiencing breastfeeding difficulties received an average of 5.5 cycles of chemotherapy, while mothers without difficulties received an average of 3.8 cycles; (2) mothers with breastfeeding difficulties received their first chemotherapy cycle an average of 3.4 weeks earlier during pregnancy. Of the 9 women treated with taxanes, 7 experienced breastfeeding difficulties.

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Docetaxel trihydrate (10 nM) induces cytotoxicity in intestinal epithelial cells IEC-6, reducing cell viability by 45% after 24 hours, while Wee1 overexpression exacerbates this toxicity (reducing cell viability by 68%) [3]
- In SD rats, docetaxel trihydrate (10 mg/kg IV) causes mild to moderate intestinal damage (villous shortening, epithelial cell apoptosis), with more severe damage when administered at ZT12 (nighttime) [3]
- No significant liver or kidney histopathological abnormalities were observed in rats treated with docetaxel trihydrate (10 mg/kg IV) [4]
- docetaxel trihydrate does not cause significant weight loss in rats, ≤4% at the treatment dose [3][4]

[1]. The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells. PeerJ. 2016 Jun 29;4:e2168.

[2]. DNA microarray reveals different pathways responding to paclitaxel and docetaxel in non-small cell lung cancer cell line. Int J Clin Exp Pathol. 2013 Jul 15;6(8):1538-48.

[3]. Involvement of Wee1 in the circadian rhythm dependent intestinal damage induced by docetaxel. J Pharmacol Exp Ther. 2013 Oct;347(1):242-8.

[4]. Non-linear pharmacokinetics of piperine and its herb-drug interactions with docetaxel in Sprague-Dawley rats. J Pharm Biomed Anal. 2016 Sep 5;128:286-93.

Docetaxel trihydrate is the trihydrate form of docetaxel. It is used to treat breast cancer, ovarian cancer, and non-small cell lung cancer, and in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer. It is an antitumor drug. It is a hydrate and also a secondary α-hydroxy ketone. It contains a homolog of anhydrous docetaxel.
Docetaxel is a semi-synthetic second-generation taxane drug derived from a compound in the European yew (Taxus baccata). Docetaxel has potent and broad-spectrum antitumor properties; it binds to and stabilizes tubulin, thereby inhibiting microtubule depolymerization, leading to cell cycle arrest in the G2/M phase and ultimately cell death. This drug also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and exhibits immunomodulatory and pro-inflammatory properties by inducing various inflammatory mediators. Docetaxel has been investigated for use as a radiosensitizer. (NCI04)
A semi-synthetic analogue of paclitaxel, used to treat locally advanced or metastatic breast cancer and non-small cell lung cancer.
See also: Docetaxel (note moved to).

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Drug Indications
Breast Cancer: Taxespira, in combination with doxorubicin and cyclophosphamide, is indicated for adjuvant therapy in patients with operable lymph node-positive breast cancer and operable lymph node-negative breast cancer. For patients with operable lymph node-negative breast cancer, adjuvant therapy should be limited to those meeting the internationally recognized criteria for first-line chemotherapy for early breast cancer. Taxespira in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy. Taxespira monotherapy is indicated for patients with locally advanced or metastatic breast cancer who have failed cytotoxic therapy. Previous chemotherapy should include anthracyclines or alkylating agents. Taxespira in combination with trastuzumab is indicated for the treatment of patients with HER2-overexpressing metastatic breast cancer who have not previously received chemotherapy for metastatic disease. Taxespira in combination with capecitabine is indicated for patients with locally advanced or metastatic breast cancer who have failed cytotoxic chemotherapy. Prior treatment should include anthracyclines. Non-small cell lung cancer: Taxespira is indicated for patients with locally advanced or metastatic non-small cell lung cancer who have failed prior chemotherapy. Taxespira in combination with cisplatin is indicated for patients with unresectable locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this disease. Taxespira in combination with prednisone or prednisolone is indicated for patients with hormone-refractory metastatic prostate cancer. Taxespira in combination with cisplatin and 5-fluorouracil is indicated for patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not previously received chemotherapy for metastatic disease. Docetaxel (Taxespira) in combination with cisplatin and 5-fluorouracil is indicated for induction therapy in patients with locally advanced head and neck squamous cell carcinoma.
Docetaxel trihydrate is a microtubule stabilizer taxane chemotherapy drug, a trihydrate form of docetaxel with stable pharmacological activity[1][2].
Its antitumor mechanisms include regulation of cell cycle-related genes (p21, GADD45α, CCNB1), activation of caspase-dependent apoptosis, and induction of G2/M phase cell cycle arrest by stabilizing microtubules[1][2].
Docetaxel trihydrate exhibits synergistic cytotoxicity with ghrelin in prostate cancer cells, supporting combination therapy strategies[1].
It interacts with piperine in vivo, leading to reduced clearance and thus increased exposure to docetaxel trihydrate, which may affect therapeutic efficacy. The intestinal toxicity of docetaxel trihydrate is related to circadian rhythms, with greater intestinal damage in rats when administered at night (ZT12)[3]. Clinically, it is indicated for the treatment of prostate cancer, non-small cell lung cancer, and other solid tumors[1][2].

C43H53NO14.3H2O

861.93

861.378

C, 59.92; H, 6.90; N, 1.63; O, 31.55

148408-66-6

Docetaxel;114977-28-5;Docetaxel-d5 trihydrate

148123

White to off-white solid powder

1.37 g/cm3

1016.9ºC at 760 mmHg

186-192ºC

568.8ºC

0mmHg at 25°C

3.457

8

17

13

61

1660

11

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)O.O.O.O

XCDIRYDKECHIPE-QHEQPUDQSA-N

InChI=1S/C43H53NO14.3H2O/c1-22-26(55-37(51)32(48)30(24-15-11-9-12-16-24)44-38(52)58-39(3,4)5)20-43(53)35(56-36(50)25-17-13-10-14-18-25)33-41(8,34(49)31(47)29(22)40(43,6)7)27(46)19-28-42(33,21-54-28)57-23(2)45;;;/h9-18,26-28,30-33,35,46-48,53H,19-21H2,1-8H3,(H,44,52);3*1H2/t26-,27-,28+,30-,31+,32+,33-,35-,41+,42-,43+;;;/m0.../s1

[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,9,12-trihydroxy-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;trihydrate

RP56976 (NSC 628503) Trihydrate; RP56976; NSC 628503; RP-56976; NSC628503; RP 56976; Docetaxel hydrate; XRP6976; Docetaxel (Trihydrate); Docetaxel (as trihydrate); RP 56976; CHEBI:59809; NSC-628503; Docetaxel trihydrate, Trade name: Taxotere.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.90 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (2.90 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (2.90 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: ≥ 2.08 mg/mL (2.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 5: ≥ 2.08 mg/mL (2.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 6: ≥ 2.08 mg/mL (2.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)