Cabazitaxel-d6
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MedKoo CAT#: 200585a

CAS#: 183133-96-2

Description: Cabazitaxel-d6 is a deuterium labeled cabazitaxel. 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).


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MedKoo#200585a: d6 - Cabazitaxel,purity > 98%, is in stock. The same day shipping out after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 200585a
Name: Cabazitaxel-d6
CAS#: 183133-96-2
Chemical Formula: C45H51D6NO14
Exact Mass: 841.41557
Molecular Weight: 841.97
Elemental Analysis: C, 64.19; H, 7.54; N, 1.66; O, 26.60


Synonym: dimethoxydocetaxeld-6; deuteriumlabeled cabazitaxel.

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-bis(methoxy-d3)-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-YHVGWTKXSA-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/i9D3,10D3

SMILES Code: O=C(O[C@@H]([C@@]1([H])[C@@]2(C)[C@@H](OC([2H])([2H])[2H])C[C@H]3OC[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([2H])([2H])[2H])C2=O)C6=CC=CC=C6


Technical Data

Appearance:
white solid powder

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

Certificate of Analysis:

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

1: Abidi A. Cabazitaxel: A novel taxane for metastatic castration-resistant prostate cancer-current implications and future prospects. J Pharmacol Pharmacother. 2013 Oct;4(4):230-237. Review. PubMed PMID: 24250198; PubMed Central PMCID: PMC3825997.

2: Kearns B, Lloyd Jones M, Stevenson M, Littlewood C. Cabazitaxel for the second-line treatment of metastatic hormone-refractory prostate cancer: a NICE single technology appraisal. Pharmacoeconomics. 2013 Jun;31(6):479-88. doi: 10.1007/s40273-013-0050-9. Review. PubMed PMID: 23580356.

3: Keating GM. Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer. Drugs Aging. 2013 May;30(5):359-65. doi: 10.1007/s40266-013-0078-8. Review. PubMed PMID: 23532557.

4: Cheetham P, Petrylak DP. Tubulin-targeted agents including docetaxel and cabazitaxel. Cancer J. 2013 Jan-Feb;19(1):59-65. doi: 10.1097/PPO.0b013e3182828d38. Review. PubMed PMID: 23337758.

5: Yap TA, Pezaro CJ, de Bono JS. Cabazitaxel in metastatic castration-resistant prostate cancer. Expert Rev Anticancer Ther. 2012 Sep;12(9):1129-36. doi: 10.1586/era.12.88. Review. PubMed PMID: 23098113.

6: Malhotra M, Dhingra R, Sharma T, Deep A, Narasimhan B, Phogat P, Sharma PC. Cabazitaxel: a novel drug for hormone-refractory prostate cancer. Mini Rev Med Chem. 2013 May 1;13(6):915-20. Review. PubMed PMID: 22950608.

7: Doyle-Lindrud S. Managing side effects of the novel taxane cabazitaxel in castrate-resistant prostate cancer. Clin J Oncol Nurs. 2012 Jun 1;16(3):286-91. doi: 10.1188/12.CJON.286-291. Review. PubMed PMID: 22641321.

8: Pean E, Demolis P, Moreau A, Hemmings RJ, O'Connor D, Brown D, Shepard T, Abadie E, Pignatti F. The European Medicines Agency review of cabazitaxel (Jevtana®) for the treatment of hormone-refractory metastatic prostate cancer: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist. 2012;17(4):543-9. doi: 10.1634/theoncologist.2011-0364. Epub 2012 Apr 3. Review. PubMed PMID: 22477727; PubMed Central PMCID: PMC3336839.

9: Villanueva C, Bazan F, Kim S, Demarchi M, Chaigneau L, Thiery-Vuillemin A, Nguyen T, Cals L, Dobi E, Pivot X. Cabazitaxel: a novel microtubule inhibitor. Drugs. 2011 Jul 9;71(10):1251-8. doi: 10.2165/11591390-000000000-00000. Review. Erratum in: Drugs. 2011 Sep 10;71(13):1720. PubMed PMID: 21770474.

10: Paller CJ, Antonarakis ES. Cabazitaxel: a novel second-line treatment for metastatic castration-resistant prostate cancer. Drug Des Devel Ther. 2011 Mar 10;5:117-24. doi: 10.2147/DDDT.S13029. Review. Erratum in: Drug Des Devel Ther. 2011;5:183. PubMed PMID: 21448449; PubMed Central PMCID: PMC3063116.