当在没有辐射的情况下应用于 4T1 细胞时，卡巴他赛 (100 μg/mL) 的细胞毒性作用为 70.8%。卡帕他赛 (100 μg/mL) 的抗增殖活性为 56.2%，表现出浓度依赖性的抗增殖作用[1]。

虽然卡帕他赛（10 mg/kg，静脉注射）会造成一些肝脏和肾脏损伤，但可以通过将其与 Ans 结合来预防。与对照组相比，AN-ICG-CBX和AN-CBX处理的小鼠体重略有下降，而游离CBX处理的小鼠体重则显着下降[1]。

Absorption, Distribution and Excretion
Based on the population pharmacokinetic analysis, after an intravenous dose of cabazitaxel 25 mg/m2 every three weeks, the mean Cmax in patients with metastatic prostate cancer was 226 ng/mL (CV 107%) and was reached at the end of the one-hour infusion (Tmax). The mean AUC in patients with metastatic prostate cancer was 991 ng x h/mL (CV 34%). No major deviation from the dose proportionality was observed from 10 to 30 mg/m2 in patients with advanced solid tumours.
After a one-hour intravenous infusion [¹⁴C]-cabazitaxel 25 mg/m², approximately 80% of the administered dose was eliminated within two weeks. Cabazitaxel is mainly excreted in the feces as numerous metabolites (76% of the dose), while renal excretion of cabazitaxel and metabolites account for 3.7% of the dose (2.3% as unchanged drug in urine). Around 20 metabolites of cabazitaxel are excreted into human urine and feces.
Steady-state volume of distribution (V_ss) was 4,864 L (2,643 L/m² for a patient with a median BSA of 1.84 m²).
Based on the population pharmacokinetic analysis, cabazitaxel has a plasma clearance of 48.5 L/h (CV 39%; 26.4 L/h/m² for a patient with a median BSA of 1.84 m²) in patients with metastatic prostate cancer.

---

Metabolism / Metabolites
More than 95% of cabazitaxel is extensively metabolized in the liver. CYP3A4 and CYP3A5 are responsible for 80% to 90% of drug metabolism, while CYP2C8 is involved to a lesser extent. While cabazitaxel is the main circulating moiety in human plasma, seven metabolites have been detected in plasma, including three active metabolites arising from O-demethylation - [docetaxel], RPR112698, and RPR123142. The main metabolite accounts for 5% of total cabazitaxel exposure.

---

Biological Half-Life
Following a one-hour intravenous infusion, plasma concentrations of cabazitaxel can be described by a three-compartment pharmacokinetic model with α-, β-, and γ- half-lives of four minutes, two hours, and 95 hours, respectively.

Hepatotoxicity
In the clinical trials and open label studies of cabazitaxel in metastatic prostate cancer, serum enzyme elevations were usually not mentioned and hepatic adverse events did not appear in lists of serious adverse events. The product label for cabazitaxel states that elevations of serum ALT and AST above 5 times ULN occur in less than 1% of treated patients. Cabazitaxel has not been linked convincingly to instances of idiosyncratic, clinically apparent liver injury with jaundice.
Cabazitaxel has been linked to acute hypersensitivity reactions that typically occur with the initial infusions and rarely with subsequent administration. Acute hypersensitivity reactions occur with the other taxanes (docetaxel and paclitaxel) which can be severe and lead to acute hepatic necrosis, multiorgan failure and death. While similar reactions have not been reported with cabazitaxel, its use has been limited. Thus, cabazitaxel has not been linked to instances of idiosyncratic, clinically apparent liver injury, but has been found to cause acute hypersensitivity reactions which have the potential to lead to acute hepatic necrosis (as have docetaxel and paclitaxel).
Likelihood score: E* (unproven, but suspected rare cause of clinically apparent liver injury).

---

Protein Binding
_In vitro_, the binding of cabazitaxel to human serum proteins was 89% to 92% and was not saturable up to 50,000 ng/mL. Cabazitaxel is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL). The _in vitro_ blood-to-plasma concentration ratio in human blood ranged from 0.90 to 0.99, indicating that cabazitaxel was equally distributed between blood and plasma.

[1]. Cabazitaxel and indocyanine green co-delivery tumor-targeting nanoparticle for improved antitumor efficacy and minimized drug toxicity. J Drug Target. 2016 Sep 9:1-29.

[2]. Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain. Nanomedicine (Lond). 2017 Sep;12(17):2083-2095.

Cabazitaxel is a tetracyclic diterpenoid that is 10-deacetylbaccatin III having O-methyl groups attached at positions 7 and 10 as well as an O-(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl group attached at position 13. Acts as a microtubule inhibitor, binds tubulin and promotes microtubule assembly and simultaneously inhibits disassembly. It has a role as an antineoplastic agent and a microtubule-stabilising agent. It is functionally related to a 10-deacetylbaccatin III.
Cabazitaxel is a taxoid synthesized from 10-deacetylbaccatin III, a compound isolated from the yew tree. As a second-generation semisynthetic microtubule inhibitor, cabazitaxel stabilizes microtubules and induces tumour cell death. Due to its low affinity for the P-glycoprotein (P-gp) efflux pump, cabazitaxel can more readily penetrate the blood–brain barrier compared to other taxanes like [paclitaxel] and [docetaxel]. Cabazitaxel is used to treat metastatic castration-resistant prostate cancer. It was first approved by the FDA on June 17, 2010. It was also approved by the EMA on March 17, 2011 and Health Canada on December 17, 2019.
Cabazitaxel is a Microtubule Inhibitor. The physiologic effect of cabazitaxel is by means of Microtubule Inhibition.
Cabazitaxel is a taxane and antineoplastic agent which is currently used in the therapy of castration-resistant metastatic prostate cancer after failure of docetaxel. Therapy with cabazitaxel has been associated with a low rate of serum enzyme elevations, but has not been linked to cases of clinically apparent acute liver injury, although it can cause severe hypersensitivity infusion reactions which in some instances can be associated with acute liver injury.
Cabazitaxel is a semi-synthetic derivative of the natural taxoid 10-deacetylbaccatin III with potential antineoplastic activity. Cabazitaxel binds to and stabilizes tubulin, resulting in the inhibition of microtubule depolymerization and cell division, cell cycle arrest in the G2/M phase, and the inhibition of tumor cell proliferation. Unlike other taxane compounds, this agent is a poor substrate for the membrane-associated, multidrug resistance (MDR), P-glycoprotein (P-gp) efflux pump and may be useful for treating multidrug-resistant tumors. In addition, cabazitaxel penetrates the blood-brain barrier (BBB).

---

Drug Indication
Cabazitaxel is indicated, in combination with [prednisone], for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a [docetaxel]-containing treatment regimen. In Europe and Canada, it can also be used in combination with [prednisolone].
Treatment of patients with hormone refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.
Jevtana in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.
Treatment of prostate cancer

---

Mechanism of Action
Microtubules are cytoskeletal polymers that regulate cell shape, vesicle transport, cell signalling, and cell division. They are made up of alpha-tubulin and beta-tubulin heterodimers. Microtubules extend toward the mitotic spindle during mitosis to allow the separation and distribution of chromosomes during cell division. Cabazitaxel binds to the N-terminal amino acids of the beta-tubulin subunit and promotes microtubule polymerization while simultaneously inhibiting disassembly: this results in the stabilization of microtubules, preventing microtubule cell division. Cabazitaxel ultimately blocks mitotic and interphase cellular functions and tumour proliferation.

---

Pharmacodynamics
Cabazitaxel demonstrates a broad spectrum of antitumour activity against advanced human tumours xenografted in mice, including intracranial human glioblastomas. Cabazitaxel has a low affinity to P-glycoprotein, allowing it to penetrate the blood-brain barrier without being subject to extensive P-gp-mediated active efflux. Cabazitaxel works against docetaxel-sensitive tumours and tumour models resistant to docetaxel and other chemotherapy drugs.

C45H57NO14

835.93

835.377

183133-96-2

Cabazitaxel-d6;1383561-29-2;Cabazitaxel-d9;1383572-19-7

9854073

White to off-white solid powder

1.3±0.1 g/cm3

870.7±65.0 °C at 760 mmHg

180 °C

480.4±34.3 °C

0.0±0.3 mmHg at 25°C

1.592

7.55

202.45

3

14

15

60

1690

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)OC)C)OC

BMQGVNUXMIRLCK-OAGWZNDDSA-N

InChI=1S/C45H57NO14/c1-24-28(57-39(51)33(48)32(26-17-13-11-14-18-26)46-40(52)60-41(3,4)5)22-45(53)37(58-38(50)27-19-15-12-16-20-27)35-43(8,36(49)34(55-10)31(24)42(45,6)7)29(54-9)21-30-44(35,23-56-30)59-25(2)47/h11-20,28-30,32-35,37,48,53H,21-23H2,1-10H3,(H,46,52)/t28-,29-,30+,32-,33+,34+,35-,37-,43+,44-,45+/m0/s1

(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-3-phenylpropanoyl)oxy)-11-hydroxy-4,6-dimethoxy-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]oxet-12-yl benzoate.

TXD 258; XRP6258; RPR116258A; TXD-258; RPR-116258A; TXD258; XRP-6258; TXD 258; XRP 6258; RPR-116258A; trade name: Jevtana.

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (2.99 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 25.0 mg/mL澄清DMSO储备液加入到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。

---

配方 2 中的溶解度: ≥ 2.5 mg/mL (2.99 mM) (饱和度未知) 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), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 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。

---

View More

配方 3 中的溶解度: ≥ 2.5 mg/mL (2.99 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 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

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。