Microtubule; tubulin polymerization; tubulin stabilizer

在细胞周期的 G2/M 期，紫杉醇（20 nM；48 小时）会导致细胞程序性死亡和停滞 [1]。紫杉醇（20 nM；48 小时）可诱导 p53 水平长期升高 [1]。 紫杉醇诱导p53水平长期升高（20 nM；48小时）。抗癌剂紫杉醇稳定微管蛋白聚合，导致细胞周期的G2/M期停滞和凋亡细胞死亡。然而，这种生长抑制和凋亡的分子机制尚不清楚。在这项研究中，我们使用具有不同雌激素受体（ER）和肿瘤抑制因子p53状态的MCF-7和MDA-MB-231人乳腺癌细胞来研究紫杉醇诱导生长抑制和凋亡的机制。用紫杉醇处理细胞导致细胞活力的时间依赖性抑制，这伴随着细胞在G2/M和亚G1凋亡区域的积聚，通过流式细胞术分析确定。此外，在用紫杉醇处理后，观察到两种细胞系中的染色质凝缩、DNA梯状结构形成和聚ADP核糖聚合酶（PARP）的蛋白水解切割，表明发生了凋亡细胞死亡。使用经紫杉醇处理的MCF-7和MDA-MB-231细胞的全细胞裂解物进行的蛋白质印迹分析表明，紫杉醇处理以时间依赖的方式抑制了细胞周期蛋白A和细胞周期蛋白B1蛋白的表达。紫杉醇对紫杉醇诱导的细胞生长和凋亡的抑制作用也与Wee1激酶表达的下调和细胞周期蛋白依赖性激酶抑制剂p21WAF/CIP1活性的显著诱导有关。此外，紫杉醇提高了两种细胞系中p21启动子的活性。这些发现表明，紫杉醇诱导的人乳腺癌细胞G2/M期阻滞和凋亡是通过p21的ER和p53非依赖性上调介导的[1]。

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用脉冲紫杉醇暴露处理的两种肿瘤细胞系都表现出大量细胞发生凋亡，但与连续紫杉醇暴露相比，在细胞周期的G2/M期停滞的细胞要少得多。短期暴露于紫杉醇也会诱导IkappaBα的磷酸化和降解，进而导致两种细胞系中NF-kappaB的激活。发现Parthenolide抑制紫杉醇诱导的NF-kappaB/IkappaB信号通路的激活以及凋亡细胞死亡。结论：这些发现表明，紫杉醇诱导的细胞凋亡可能独立于之前的G2/M期阻滞而发生，并由NF-kappaB/IkappaB信号通路介导或调节。[2]

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为了解决紫杉醇在抗凋亡蛋白Bcl-2存在下的疗效争议，我们研究了内质网中储存的钙作为一种潜在因素。我们的研究结果表明，ER钙库是紫杉醇和Bcl-2蛋白的共同靶点。紫杉醇直接与内质网结合，刺激钙释放到细胞质中，有助于诱导细胞凋亡。然而，Bcl-2的表达抑制了细胞内质网钙释放的促凋亡反应，从而抑制了癌症细胞发生凋亡的易感性。根据剂量的不同，紫杉醇诱导的刺激作用可以克服Bcl-2介导的对内质网钙释放的抑制作用，从而减弱Bcl-2对细胞凋亡的抵抗力。我们的发现首次证明内质网钙在Bcl-2存在的情况下对紫杉醇的疗效起着关键作用，从而深入了解了复杂但关键的紫杉醇-钙-Bcl-2关系，这可能会影响乳腺癌症的治疗[4]。

在低剂量紫杉醇组中，紫杉醇（1-20mg/kg；腹腔注射；每两天一次，共5个周期）显著增加了肝转移的风险，同时对潜在肿瘤的生长影响很小。在此，我们报道了低剂量的紫杉醇增强小鼠模型中乳腺癌症细胞向肝脏的转移。我们使用微阵列分析来研究用低剂量或临床相关的高剂量紫杉醇治疗的侵袭性癌症细胞的基因表达模式。我们还研究了低剂量紫杉醇对体外和体内细胞迁移、侵袭和转移的影响。结果表明，低剂量紫杉醇促进炎症，启动上皮间质转化，从而增强肿瘤细胞在体外的迁移和侵袭。这些作用可以通过抑制NF-κB来逆转。此外，低剂量的紫杉醇促进了小鼠异种移植物的肝转移，这与宿主肝脏中雌激素代谢的变化有关。总之，这些发现揭示了紫杉醇对乳腺癌症细胞活性的矛盾和剂量依赖性影响，并建议在治疗过程中更多地考虑与低浓度紫杉醇相关的潜在不良影响[3]。

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本研究的目的是检验化疗诱导的周围神经病变（CIPN）的独特表现将反映在皮肤神经元亚群细胞内钙浓度（[Ca（2+）]i）调节的特定变化模式中的预测。为了验证这一预测，我们描述了与紫杉醇给药（2mg/kg，静脉注射，每隔一天一次，持续四天）相关的机械伤害性阈值的变化模式，以及神经支配靶点和紫杉醇治疗对推定的伤害性和非伤害性神经元亚群中[Ca（2+）]i调节的影响。用逆行示踪剂鉴定了支配后爪无毛和多毛皮肤以及大腿的神经元，并使用fura-2来评估[Ca（2+）]i的变化。紫杉醇与后爪无毛皮肤受到刺激时机械伤害性阈值的持续降低有关，但与后爪或大腿的多毛皮肤无关。然而，在假定的伤害性和非伤害性神经元中，治疗后支配大腿的神经元的静息[Ca（2+）]i显著降低。在假定的非伤害性大腿神经元中，去极化诱发的Ca（2+）瞬变的幅度也较低。更有趣的是，虽然紫杉醇对推定的非伤害性神经元中的静息或去极化诱发的Ca（2+）瞬变没有可检测的影响，但在推定的伤害性神经元里，诱发的Ca。这些结果表明，仅外周神经长度并不能解释CIPN症状的选择性分布。相反，他们认为CIPN的症状反映了治疗的毒性作用与受到有害影响的神经元的独特特性之间的相互作用[6]。

细胞凋亡分析[1]
细胞类型： MCF-7、MDA-MB-231 细胞
测试浓度： 20 nM
孵育持续时间： 48 小时
实验结果：诱导程序性细胞死亡。

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细胞周期分析[1]
细胞类型： MCF-7、MDA-MB -231 细胞
测试浓度： 20 nM
孵育时间：48小时
实验结果：>60%的MCF-7细胞和50%的MDA-MB-231细胞被24小时治疗后的G2/M期。

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蛋白质印迹分析[1]
细胞类型： MCF-7 细胞（含有野生型 p53）
测试浓度： 20 nM
孵育持续时间： 48 小时
实验结果： 诱导 p53 水平持续增加。

Animal/Disease Models: MDA-231 xenograft-bearing mice[3]
Doses: 1, 20 mg/kg
Route of Administration: intraperitoneal (ip)injection; five cycles (1 time/2 days)
Experimental Results: Liver metastases were obviously induced in the low-PTX (1 mg /kg) group with little influence on primary tumor growth compared with high-PTX group.《hr Paclitaxel treatment[6]
One week following the DiI injection, rats were anesthetized with isofluorane and injected into the tail vein with 2 mg/kg paclitaxel or its vehicle (1:1:23, cremophor EL:ethanol:0.9% saline). The tail vein injection was repeated three more times every other day for a total of four injections.

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Primary tumor growth and metastasis detection in vivo[3]
Specific pathogen free (SPF) nude mice were used. MDA-231 cells (1 × 106) were subcutaneously transplanted. After the formation of primary tumors (diameter > 5 mm), the mice were randomly grouped (10 mice per group) and different doses of PTX (paclitaxel) were diluted with normal saline and administrated by intraperitoneal injection (1 time/2 days). After five cycles of treatment, the mice were euthanized. The primary tumor growth and metastatic intensities were then measured, and images were captured.

Absorption, Distribution and Excretion
When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the maximum plasma concentration (Cmax) is 195 ng/mL, while the AUC is 6300 ng•h/mL.
In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered in the urine.
227 to 688 L/m^2 [apparent volume of distribution at steady-state, 24 hour infusion]
21.7 L/h/m2 [Dose 135 mg/m2, infusion duration 24 h]
23.8 L/h/m2 [Dose 175 mg/m2, infusion duration 24 h]
7 L/h/m2 [Dose 135 mg/m2, infusion duration 3 h]
12.2 L/h/m2 [Dose 175 mg/m2, infusion duration 3 h]
Paclitaxel bound to nanoparticles of the serum protein albumin is delivered via endothelial transport mediated by albumin receptors, and the resulting concentration of paclitaxel in tumor cells is increased compared with that achieved using an equivalent dose of conventional paclitaxel. Like conventional paclitaxel, albumin-bound paclitaxel has a large volume of distribution. Following 30-minute or 3-hour IV infusion of 80-375 mg/sq m albumin-bound paclitaxel, the volume of distribution averaged 632 L/sq m. The volume of distribution of albumin-bound paclitaxel 260 mg/sq m by 30-minute IV infusion was 53% larger than the volume of distribution of conventional paclitaxel 175 mg/sq m by 3-hour IV infusion. /Paclitaxel (albumin-bound)/
Following IV administration, paclitaxel is widely distributed into body fluids and tissues. Paclitaxel has a large volume of distribution that appears to be affected by dose and duration of infusion. Following administration of paclitaxel doses of 135 or 175 mg/sq m by IV infusion over 24 hours in patients with advanced ovarian cancer, the mean apparent volume of distribution at steady state ranged from 227-688 L/sq m. The steady-state volume of distribution ranged from 18.9-260 L/sq m in children with solid tumors or refractory leukemia receiving paclitaxel 200-500 mg/sq m by 24-hour IV infusion. Paclitaxel does not appear to readily penetrate the CNS, but paclitaxel has been detected in ascitic fluid following IV infusion of the drug. It is not known whether paclitaxel is distributed into human milk, but in lactating rats given radiolabeled paclitaxel, concentrations of radioactivity in milk were higher than those in plasma and declined in parallel with plasma concentrations of the drug.
For the dose range 80-375 mg/sq m, increase in dose of albumin-bound paclitaxel was associated with a proportional increase in AUC.354 The duration of infusion did not affect the pharmacokinetic disposition of albumin-bound paclitaxel. Following 30-minute or 3-hour IV infusion of albumin-bound paclitaxel 260 mg/sq m, the peak plasma concentration averaged 18,741 ng/mL. /Paclitaxel (albumin-bound)/
Peak plasma concentrations and areas under the plasma concentration-time curve (AUCs) following IV administration of paclitaxel exhibit marked interindividual variation. Plasma concentrations of paclitaxel increase during continuous IV administration of the drug and decline immediately following completion of the infusion. Following 24-hour IV infusion of paclitaxel at doses of 135 or 175 mg/sq m in patients with advanced ovarian cancer, peak plasma concentrations averaged 195 or 365 ng/mL, respectively; the increase in dose (30%) was associated with a disproportionately greater increase in peak plasma concentration (87%), but the increase in AUC was proportional. When paclitaxel was administered by continuous IV infusion over 3 hours at doses of 135 or 175 mg/sq m in patients with advanced ovarian cancer, peak plasma concentrations averaged 2.17 or 3.65 ug/mL, respectively; the increase in dose (30%) was associated with disproportionately greater increases in peak plasma concentration (68%) and AUC (89%).
For more Absorption, Distribution and Excretion (Complete) data for TAXOL (8 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hepatic. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4.
Paclitaxel is extensively metabolized in the liver. Metabolism of paclitaxel to its major metabolite, 6alpha-hydroxypaclitaxel, is mediated by cytochrome P-450 isoenzyme CYP2C8,1 185 187 202 354 while metabolism to 2 of its minor metabolites, 3'-p-hydroxypaclitaxel and 6alpha,3'-p-dihydroxypaclitaxel, is catalyzed by CYP3A4.
The elimination of nonradioactive taxol in bile and urine was investigated in the rat after administration via the caudal vein (10 mg/kg). As in humans, no metabolites of taxol were detected by HPLC in rat urine, and only 10% of the injected taxol was recovered in urine over a 24 hr period. In contrast, 11.5% and 29% of the injected taxol was recovered in rat bile as unchanged taxol and metabolites, respectively. Among the nine taxol metabolites detected by HPLC, the side chain at C13, which is required for pharmacological activity, had been removed in only one minor metabolite, baccatin III. The chemical structures of the two major hydroxylated metabolites were determined by MS (fast atom bombardment and desorption chemical ionization) and (1)H NMR spectroscopy. One was a taxol derivative hydroxylated on the phenyl group at C3 of the side chain at C13, while the other corresponded to a taxol derivative hydroxylated in the m-position on the benzoate of the side chain at C2. Although these two major taxol metabolites were as active as taxol in preventing cold microtubule disassembly, they were, respectively, 9 and 39 times less cytotoxic as taxol on in vitro L1210 leukemia growth. These results show for the first time that there is a significant hepatic metabolism of taxol.
To investigate how taxane's substituents at C3' affect its metabolism, ... the metabolism of cephalomannine and paclitaxel, a pair of analogs that differ slightly at the C3' position /was compared/. After cephalomannine was incubated with human liver microsomes in an NADPH-generating system, two monohydroxylated metabolites (M1 and M2) were detected by liquid chromatography/tandem mass spectrometry. C4'' (M1) and C6alpha (M2) were proposed as the possible hydroxylation sites, and the structure of M1 was confirmed by (1)H NMR. Chemical inhibition studies and assays with recombinant human cytochromes P450 (P450s) indicated that 4''-hydroxycephalomannine was generated predominantly by CYP3A4 and 6alpha-hydroxycephalomannine by CYP2C8. The overall biotransformation rate between paclitaxel and cephalomannine differed slightly (184 vs. 145 pmol/min/mg), but the average ratio of metabolites hydroxylated at the C13 side chain to C6alpha for paclitaxel and cephalomannine varied significantly (15:85 vs. 64:36) in five human liver samples. Compared with paclitaxel, the major hydroxylation site transferred from C6alpha to C4'', and the main metabolizing P450 changed from CYP2C8 to CYP3A4 for cephalomannine. In the incubation system with rat or minipig liver microsomes, only 4''-hydroxycephalomannine was detected, and its formation was inhibited by CYP3A inhibitors. Molecular docking by AutoDock suggested that cephalomannine adopted an orientation in favor of 4''-hydroxylation, whereas paclitaxel adopted an orientation favoring 3'-p-hydroxylation. Kinetic studies showed that CYP3A4 catalyzed cephalomannine more efficiently than paclitaxel due to an increased V(m). Our results demonstrate that relatively minor modification of taxane at C3' has major consequence on the metabolism.
Hepatic. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4.
Route of Elimination: In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered in the urine.
Half Life: When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the elimination half=life is 52.7 hours.

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Biological Half-Life
When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the elimination half=life is 52.7 hours.
5.3-17.4 hours after 1 and 6 hour infusions at dosing levels of 15-275 mg/sq m
Following IV infusion of paclitaxel over periods ranging from 6-24 hours in adults with malignancy, plasma concentrations of paclitaxel appeared to decline in a biphasic manner in some studies, with an average distribution half-life of 0.34 hours and an average elimination half-life of 5.8 hours. However, additional studies, particularly those in which paclitaxel is administered over shorter periods of infusion, show that the drug exhibits nonlinear pharmacokinetic behavior. In patients receiving paclitaxel 175 mg/sq m administered by 3-hour IV infusion, the distribution half-life averages 0.27 hours and the elimination half-life averages 2.33 hours.
Following 30-minute or 3-hour IV infusion of 80-375 mg/sq m albumin-bound paclitaxel, ... terminal half-life albumin-bound paclitaxel was about 27 hours. ... /Paclitaxel (albumin-bound)/

Hepatotoxicity
Paclitaxel has been associated with serum aminotransferase elevations in 7% to 26% of patients, but values greater than 5 times the upper limit of normal (ULN) in only 2% of those receiving the highest doses. Similar rates of alkaline phosphatase elevations and occasional mild bilirubin elevations also occur. The abnormalities are usually asymptomatic, mild and self-limited, rarely requiring dose modification or discontinuation. Paclitaxel has not been linked convincingly to instances of delayed, idiosyncratic clinically apparent liver injury with jaundice. However, the hypersensitivity reactions that occur with infusions of paclitaxel can be severe and accompanied by acute hepatic necrosis. The liver injury may be relatively mild and anicteric (Case 1), but can also be severe with rapid onset of multiorgan failure and death. At least one instance of acute liver failure following a hypersensitivity reaction to paclitaxel has been published in the literature and recent modifications of the product labels for paclitaxel and docetaxel mention the occurrence of toxic deaths following severe infusion reactions. Because paclitaxel is often given with other antineoplastic agents, liver injury arising during therapy cannot always be reliably attributed to paclitaxel rather than to other specific agents. Furthermore, paclitaxel in combination with other anticancer agents may be associated with reactivation of hepatitis B, increased risk of opportunistic viral infections, sinusoidal obstruction syndrome or sepsis, any of which can cause liver test abnormalities or clinically apparent liver injury.
Likelihood score: D (possible cause of acute hepatic necrosis associated with a hypersensitivity reaction to the initial infusions).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence. Some have suggested a breastfeeding abstinence period of 6 to 10 days, but more recent pharmacokinetic modeling using a worst-case scenario suggests that 6 days would be adequate to minimize both systemic and gut toxicity after the colostral phase.
Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant than typical mothers.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 9 women who received a taxane-containing regimen, 7 had breastfeeding difficulties.

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Protein Binding
89%-98% bound to plasma protein. The presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel.

[1]. Paclitaxel-induced growth arrest and apoptosis is associated with the upregulation of the Cdk inhibitor, p21WAF1/CIP1, in human breast cancer cells. Oncol Rep. 2012 Dec;28(6):2163-9.

[2]. Paclitaxel-induced apoptosis may occur without a prior G2/M-phase arrest. Anticancer Res. 2004 Jan-Feb;24(1):27-36.

[3]. Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model. FEBS J. 2016 Aug;283(15):2836-52.

[4]. Paclitaxel attenuates Bcl-2 resistance to apoptosis in breast cancer cells through an endoplasmic reticulum-mediated calciumrelease in a dosage dependent manner. Biochem Biophys Res Commun. 2013 Feb 13. pii: S0006-291X(13)00259-3.

[5]. Low dose paclitaxel reduces S100A4 nuclear import to inhibit invasion and hematogenous metastasis of cholangiocarcinoma. Cancer Res. 2016 Jun 21.

[6]. Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model. FEBS J. 2016 Jun 16.

[7]. Sensory neuron subpopulation-specific dysregulation of intracellular calcium in a rat model of chemotherapy-induced peripheral neuropathy. Neuroscience. 2015 Aug 6;300:210-8.

[8]. E7080 enhances the antitumor effects of paclitaxel in anaplastic thyroid cancer. Am J Cancer Res. 2017 Apr 1;7(4):903-912.

Paclitaxel can cause developmental toxicity, female reproductive toxicity and male reproductive toxicity according to state or federal government labeling requirements.
Taxol appears as needles (from aqueous methanol) or fine white powder. An anti-cancer drug.
Paclitaxel is a tetracyclic diterpenoid isolated originally from the bark of the Pacific yew tree, Taxus brevifolia. It is a mitotic inhibitor used in cancer chemotherapy. Note that the use of the former generic name 'taxol' is now limited, as Taxol is a registered trade mark. It has a role as a microtubule-stabilising agent, a metabolite, a human metabolite and an antineoplastic agent. It is a tetracyclic diterpenoid and a taxane diterpenoid. It is functionally related to a baccatin III.
Paclitaxel is a chemotherapeutic agent marketed under the brand name Taxol among others. Used as a treatment for various cancers, paclitaxel is a mitotic inhibitor that was first isolated in 1971 from the bark of the Pacific yew tree which contains endophytic fungi that synthesize paclitaxel. It is available as an intravenous solution for injection and the newer formulation contains albumin-bound paclitaxel marketed under the brand name Abraxane.
Paclitaxel is a Microtubule Inhibitor. The physiologic effect of paclitaxel is by means of Microtubule Inhibition.
Paclitaxel is an antineoplastic agent which acts by inhibitor of cellular mitosis and which currently plays a central role in the therapy of ovarian, breast, and lung cancer. Therapy with paclitaxel has been associated with a low rate of serum enzyme elevations, but has not been clearly linked to cases of clinically apparent acute liver injury.
Paclitaxel has been reported in Aspergillus ochraceopetaliformis, Aspergillus versicolor, and other organisms with data available.
Paclitaxel is a compound extracted from the Pacific yew tree Taxus brevifolia with antineoplastic activity. Paclitaxel binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. This agent also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). (NCI04)
Nab-paclitaxel is a Cremophor EL-free, albumin-stabilized nanoparticle formulation of the natural taxane paclitaxel with antineoplastic activity. Paclitaxel binds to and stabilizes microtubules, preventing their depolymerization and so inhibiting cellular motility, mitosis, and replication. This formulation solubilizes paclitaxel without the use of the solvent Cremophor, thereby permitting the administration of larger doses of paclitaxel while avoiding the toxic effects associated with Cremophor.
A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS brevifolia. It stabilizes microtubules in their polymerized form leading to cell death. ABI-007 (Abraxane) is the latest attempt to improve upon paclitaxel, one of the leading chemotherapy treatments. Both drugs contain the same active agent, but Abraxane is delivered by a nanoparticle technology that binds to albumin, a natural protein, rather than the toxic solvent known as Cremophor. It is thought that delivering paclitaxel with this technology will cause fewer hypersensitivity reactions and possibly lead to greater drug uptake in tumors. Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel.
See also: Paclitaxel Ceribate (is active moiety of); Paclitaxel Poliglumex (is active moiety of); 7-Acetyltaxol (annotation moved to).

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Drug Indication
Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast. Abraxane® is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer.
FDA Label
Apealea in combination with carboplatin is indicated for the treatment of adult patients with first relapse of platinum‑sensitive epithelial ovarian cancer , primary peritoneal cancer and fallopian tube cancer .
Abraxane monotherapy is indicated for the treatment of metastatic breast cancer in adult patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. Abraxane in combination with gemcitabine is indicated for the first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas. Abraxane in combination with carboplatin is indicated for the first-line treatment of non-small cell lung cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy.
Pazenir monotherapy is indicated for the treatment of metastatic breast cancer in adult patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. Pazenir in combination with carboplatin is indicated for the first-line treatment of non-small cell lung cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy.
Paxene is indicated for the treatment of patients with: • advanced AIDS-related Kaposi's sarcoma (AIDS-KS) who have failed prior liposomal anthracycline therapy; • metastatic carcinoma of the breast (MBC) who have failed, or are not candidates for standard anthracycline-containing therapy; • advanced carcinoma of the ovary (AOC) or with residual disease (> 1 cm) after initial laparotomy, in combination with cisplatin as first-line treatment; • metastatic carcinoma of the ovary (MOC) after failure of platinum-containing combination therapy without taxanes as second-line treatment; • non-small cell lung carcinoma (NSCLC) who are not candidates for potentially curative surgery and/or radiation therapy, in combination with cisplatin. Limited efficacy data supports this indication (see section 5. 1).
Treatment of soft tissue sarcoma
Treatment of solid malignant tumours

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Mechanism of Action
Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
Evidence suggests that paclitaxel also may induce cell death by triggering apoptosis. In addition, paclitaxel and docetaxel enhance the effects of ionizing radiation, possibly by blocking cells in the G2 phase, the phase of the cell cycle in which cells are most radiosensitive.
Paclitaxel is an antimicrotubule antineoplastic agent. Unlike some other common antimicrotubule agents (e.g., vinca alkaloids, colchicine, podophyllotoxin), which inhibit microtubule assembly, paclitaxel and docetaxel (a semisynthetic taxoid) promote microtubule assembly. Microtubules are organelles that exist in a state of dynamic equilibrium with their components, tubulin dimers. They are an essential part of the mitotic spindle and also are involved in maintenance of cell shape and motility, and transport between organelles within the cell. By binding in a reversible, concentration-dependent manner to the beta-subunit of tubulin at the N-terminal domain, paclitaxel enhances the polymerization of tubulin, the protein subunit of the spindle microtubules, even in the absence of factors that are normally required for microtubule assembly (e.g., guanosine triphosphate [GTP]), and induces the formation of stable, nonfunctional microtubules. Paclitaxel promotes microtubule stability even under conditions that typically cause depolymerization in vitro (e.g., cold temperature, the addition of calcium, the presence of antimitotic drugs). While the precise mechanism of action of the drug is not understood fully, paclitaxel disrupts the dynamic equilibrium within the microtubule system and blocks cells in the late G2 phase and M phase of the cell cycle, inhibiting cell replication.
... Taxol induces tubulin polymerization and forms extremely stable and nonfunctional microtubules. Taxol has demonstrated broad activity in preclinical screening studies, and antineoplastic activity has been observed in several classically refractory tumors. These tumors include cisplatin resistant ovarian carcinoma in phase II trials and malignant melanoma and non-small cell lung carcinoma in phase I studies.

C47H51NO14

853.91

853.33

C, 66.11; H, 6.02; N, 1.64; O, 26.23

33069-62-4

Paclitaxel-d5;1129540-33-5;Paclitaxel-d5 (benzoyloxy);1261254-56-1; 33069-62-4; 186040-50-6 (ceribate); 263351-82-2 (Poliglumex); 117527-50-1 (Paclitaxel-Succinic acid)

36314

White to off-white solid powder

1.4±0.1 g/cm3

957.1±65.0 °C at 760 mmHg

213 °C (dec.)(lit.)

532.6±34.3 °C

0.0±0.3 mmHg at 25°C

1.637

7.38

221.29

4

14

14

62

1790

11

O=C(C1=CC=CC=C1)N[C@@H](C2=CC=CC=C2)[C@H](C(O[C@@H]3C(C)=C([C@@H](OC(C)=O)C([C@@]4(C)[C@]([C@@](CO5)(OC(C)=O)[C@@]5([H])C[C@@H]4O)([H])[C@@H]6OC(C7=CC=CC=C7)=O)=O)C(C)(C)[C@@]6(O)C3)=O)O

RCINICONZNJXQF-MZXODVADSA-N

InChI=1S/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)49)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37+,38-,40-,45+,46-,47+/m0/s1

(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-9-(((2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl)oxy)-12-(benzoyloxy)-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b-diyl diacetate

NSC 125973; BMS 181339-01; NSC-125973; BMS181339-01; NSC125973; BMS-181339-01; Trade name: Taxol; Taxol Konzentrat; Anzatax; Asotax; Bristaxol; Praxel; TAX.P88XT4IS4D; Paclitaxel; Taxol A; Yewtaxan; Genaxol; Plaxicel;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

配方 1 中的溶解度: ≥ 2.08 mg/mL (2.44 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.08 mg/mL (2.44 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (2.44 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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配方 4 中的溶解度: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 30 mg/mL

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配方 5 中的溶解度: 10 mg/mL (11.71 mM) in Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。

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配方 6 中的溶解度: 10 mg/mL (11.71 mM) in 50% PEG300 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。