MedKoo Cat#: 200585 Name: Cabazitaxel CAS#: 183133-96-2 Chemical Formula: C45H57NO14 Exact Mass: 835.37791 Molecular Weight: 835.93 Elemental Analysis: C, 64.66; H, 6.87; N, 1.68; O, 26.80.

Synonym: XRP6258; XRP-6258; XRP 6258; TXD 258; TXD-258; TXD258; RPR116258A; axoid XRP6258; dimethoxydocetaxel US brand name: Jevtana.

IUPAC/Chemical Name: (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.

InChi Key: BMQGVNUXMIRLCK-OAGWZNDDSA-N

InChi Code: 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

SMILES Code: O=C(O[C@@H]([C@@]1([H])[C@@]2(C)[C@@H](OC)C[C@@]3([H])OC[C@]31OC(C)=O)[C@]4(O)C[C@H](OC([C@H](O)[C@@H](NC(OC(C)(C)C)=O)C5=CC=CC=C5)=O)C(C)=C(C4(C)C)[C@@H](OC)C2=O)C6=CC=CC=C6

Technical Data

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Certificate of Analysis: View current batch of CoA

QC Data: View NMR, View HPLC, View MS

Safety Data Sheet (MSDS): View Material Safety Data Sheet (MSDS)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

Additional Information

    Chemical structure of cabazitaxel Comparing to the chemical structure of docetaxel, cabazitaxel has two more methyl groups. For this reason, cabazitaxel is also called dimethoxydocetaxel (see the following chemical structures).   Scheme 1: chemical structures of cabazitaxel and docetaxel   Cabazitaxel: Drug Description JEVTANA (cabazitaxel) is an antineoplastic agent belonging to the taxane class. It is prepared by semi-synthesis with a precursor extracted from yew needles. The chemical name of cabazitaxel is (2α,5β;,7β;,10β;,13α)-4-acetoxy-13-({(2R,3S)-3[(tertbutoxycarbonyl) amino]-2-hydroxy-3-phenylpropanoyl}oxy)-1-hydroxy-7,10-dimethoxy-9oxo-5,20-epoxytax-11-en-2-yl benzoate – propan-2-one(1:1). Cabazitaxel is a white to off-white powder with a molecular formula of C45H57NO14•C3H6O and a molecular weight of 894.01 (for the acetone solvate) / 835.93 (for the solvent free). It is lipophilic, practically insoluble in water and soluble in alcohol.  JEVTANA (cabazitaxel) Injection 60 mg/1.5 mL is a sterile, non-pyrogenic, clear yellow to brownish-yellow viscous solution and is available in single-use vials containing 60 mg cabazitaxel (anhydrous and solvent free) and 1.56 g polysorbate 80. Each mL contains 40 mg cabazitaxel (anhydrous) and 1.04 g polysorbate 80. DILUENT for JEVTANA is a clear, colorless, sterile, and non-pyrogenic solution containing 13% (w/w) ethanol in water for injection, approximately 5.7 mL.  JEVTANA requires two dilutions prior to intravenous infusion. JEVTANA injection should be diluted only with the supplied DILUENT for JEVTANA, followed by dilution in either 0.9% sodium chloride solution or 5% dextrose solution.   Cabazitaxel: Mechanism of Action The taxanes act by binding to microtubules, cytoskeletal polymers composed of α-tubulin and β-tubulin heterodimers. The binding of taxanes to tubulin promotes the stabilization of GDP-bound tubulin in the microtubule resulting in inhibition of disassembly and prevention of subsequent mitosis and cell division.  Derived from the bark of yew trees, in 1992, paclitaxel was the first taxane approved by the Food and Drug Administration (FDA) as an anti-neoplastic agent. Docetaxel, a semisynthetic analog with increased potency, was approved by the FDA in 1996 for the treatment advanced breast cancer and later in 2004 for the treatment of metastatic CRPC. These earlier generation taxanes have high substrate affinity for the ATP-dependent drug efflux pump P-glycoprotein 1 (P-gp1). Therefore, P-gp1 is thought to account for, at least in part, both inherent and acquired resistance to these agents.   Cabazitaxel, also known as XRP6258, is a semi-synthetic taxane from a single diastereoisomer of 10-deacetyl baccatin III, and derived from the needles of various Taxus species. By binding to tubulin, cabazitaxel inhibits microtubule depolymerization and cell division, resulting in cell cycle arrest. This compound was selected for clinical testing due to its poor affinity for ATP-dependent drug efflux pump P-gp1, and its greater blood-brain barrier penetration compared to paclitaxel and docetaxel. Cabazitaxel has also demonstrated superior in vitro cytotoxicity compared to docetaxel in several murine and human cancer cell lines. ( source: Clinical Development of Cabazitaxel for the Treatment of Castration-Resistant Prostate Cancer . Che-Kai Tsao, Sonia Seng, William K. Oh, and Matthew D. Galsky Division of Hematology and Medical Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029, USA, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117627/ ).    

References

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