Cabazitaxel
[CAS# 183133-96-2]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Prostaglandins
• Name: Cabazitaxel
• Synonyms: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1-hydroxy-15-[(2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]oxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• Molecular Formula: C₄₅H₅₇NO₁₄
• Molecular Weight: 835.93
• CAS Registry Number: 183133-96-2
• EC Number: 680-632-7
• SMILES: 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

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 870.7±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 480.4±34.3 °C (Calc.)^*
• Solubility: DMSO: 41mg/mL (Expl.)
• Index of refraction: 1.592 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H311-H315-H317-H318-H335-H341-H360-H361-H361fd-H362-H372-H373-H400-H410
• Safety Statements: P203-P260-P261-P262-P263-P264-P264+P265-P270-P271-P272-P273-P280-P301+P317-P302+P352-P304+P340-P305+P354+P338-P316-P317-P318-P319-P321-P330-P332+P317-P333+P317-P361+P364-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Germ cell mutagenicity	Muta.	2	H341
Reproductive toxicity	Lact.	-	H362
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Acute toxicity	Acute Tox.	3	H311
Reproductive toxicity	Repr.	1B	H360
Reproductive toxicity	Repr.	1A	H360
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Skin sensitization	Skin Sens.	1	H317
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Specific target organ toxicity - single exposure	STOT SE	3	H335
Serious eye damage	Eye Dam.	1	H318

Discovery and Applications

Cabazitaxel is a semisynthetic derivative of the natural product taxol (paclitaxel), belonging to the taxane class of diterpenoid compounds. It has the molecular formula C₄₅H₅₇NO₁₄ and is characterized by a complex polycyclic structure containing an 8-membered taxane core with multiple ester and hydroxyl functional groups.

Cabazitaxel was developed to overcome resistance mechanisms associated with earlier taxanes such as paclitaxel and docetaxel. It was first approved for clinical use in the treatment of metastatic castration-resistant prostate cancer after progression on docetaxel therapy. The drug exhibits antineoplastic activity by promoting microtubule stabilization, thereby inhibiting cell division and inducing apoptosis in cancer cells.

The compound differs structurally from docetaxel by the presence of two methoxy groups at positions C7 and C10 on the taxane ring, which reduces its affinity for P-glycoprotein efflux pumps. This structural modification enhances its ability to evade multidrug resistance, allowing improved intracellular accumulation in resistant tumor cells.

Cabazitaxel is synthesized semi-synthetically from 10-deacetylbaccatin III, a natural precursor isolated from the needles of the European yew tree (*Taxus baccata*). The synthetic pathway involves selective protection and functional group manipulations to introduce the unique side chain at the C13 position, essential for its biological activity.

Pharmacologically, cabazitaxel binds to the β-tubulin subunit of microtubules, stabilizing polymerized microtubules and preventing their depolymerization. This leads to mitotic arrest at the metaphase/anaphase transition and activation of apoptosis pathways in rapidly dividing cells. Its improved pharmacokinetic profile includes better blood-brain barrier penetration and lower susceptibility to efflux mechanisms compared to earlier taxanes.

Clinically, cabazitaxel is administered intravenously, typically in combination with corticosteroids to mitigate side effects such as hypersensitivity reactions. It is associated with adverse effects including neutropenia, anemia, fatigue, and diarrhea, requiring careful patient monitoring.

In summary, cabazitaxel is a clinically important taxane derivative designed to overcome multidrug resistance in cancer therapy. Its structural modifications confer enhanced efficacy against resistant tumors, and it plays a significant role in the treatment of advanced prostate cancer and other malignancies.

References

2010. New taxane treats advanced prostate cancer. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 67(16).
DOI: 10.2146/news100052

2017. Activity of cabazitaxel in patients with metastatic castration-resistant prostate cancer after treatment with single or dual regimens of novel androgen receptor-targeting agents. Medical oncology (Northwood, London, England), 34(10).
DOI: 10.1007/s12032-017-1024-0

2017. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer—PROSELICA. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 35(28).
DOI: 10.1200/jco.2016.72.1076