Cabazitaxel

Base Information

• Chemical Name: Cabazitaxel
• CAS No.: 183133-96-2
• Deprecated CAS: 890654-44-1
• Molecular Formula: C45H57NO14
• Molecular Weight: 835.946
• Hs Code.: 29329990
• European Community (EC) Number: 680-632-7
• NSC Number: 761432
• UNII: 51F690397J
• DSSTox Substance ID: DTXSID40171389
• Nikkaji Number: J2.871.889F
• Wikipedia: Cabazitaxel
• Wikidata: Q412963
• NCI Thesaurus Code: C66937
• RXCUI: 996051
• Pharos Ligand ID: 8N87M2SWUTJ6
• Metabolomics Workbench ID: 43702
• ChEMBL ID: CHEMBL1201748
• Mol file: 183133-96-2.mol

Synonyms:cabazitaxel;jevtana;kabazitaxel

Chemical Property of Cabazitaxel

Chemical Property:

• Appearance/Colour: white powder
• Melting Point: 180 °C
• Boiling Point: 870.7±65.0 °C(Predicted)
• PKA: 11.20±0.46(Predicted)
• PSA: 202.45000
• Density: 1.31
• LogP: 4.95870
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• XLogP3: 2.7
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 14
• Rotatable Bond Count: 15
• Exact Mass: 835.37790549
• Heavy Atom Count: 60
• Complexity: 1690

Purity/Quality:

99%MIN ^*data from raw suppliers

Cabazitaxel ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1=C2C(C(=O)C3(C(CC4C(C3C(C(C2(C)C)(CC1OC(=O)C(C(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
• Isomeric 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
• Recent ClinicalTrials: Enzalutamide and Cabazitaxel in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer
• Recent EU Clinical Trials: A Phase II, Open-label Study to Assess the Efficacy, Safety, and Tolerability of AZD4635 in Combination with Durvalumab and in Combination with Cabazitaxel and Durvalumab in Patients Who Have Progressive Metastatic Castrate-Resistant Prostate Cancer (AARDVARC)
• Recent NIPH Clinical Trials: Early conversion to cabazitaxel for castration-resistant prostate cancer
• Description: In June 2010, the U.S. FDA approved cabazitaxel (also referred to as XRP6258 and RPR 116258A) in combination with the steroid prednisone for the treatment of metastatic Castration-Resistant Prostate Cancer (mCRPC) for patients who were previously treated with a docetaxelcontaining regimen for late-stage disease. Cabazitaxel is a semisynthetic analog of the natural product taxol, which is isolated from the bark of the yew tree. Cabazitaxel is a microtubule inhibitor that binds to the taxol-binding site of tubulin. Similar to other tubulin inhibitors of the taxol class, cabazitaxel inhibits microtubule disassembly resulting in mitotic blockade and cell death. Docetaxel, also a semisynthetic taxol analog, was approved by the FDA for the treatment of mCRPC in 2004. However, docetaxel is a substrate for P-gp, which is thought to contribute to the constitutive and acquired resistance of cancer cells to taxanes. Cabazitaxel has poor affinity for P-gp and showed antitumor activity in preclinical in vitro studies and in vivo tumor models that overexpress this protein. Cabazitaxel is synthesized on a commercial scale from 10-deacetylbaccatin .
• Uses: Cabazitaxel (Jevtana, XRP6258) is a semi-synthetic derivative of a natural taxoid. A novel semi-synthetic taxane with antitumor activity used for the treatment of castration-resistant prostate cancer. A microtubule inhibitor.
• Clinical Use: Cabazitaxel was developed by Sanofi-Aventis as an intravenous injectable drug for the treatment of hormone-refractory metastatic prostate cancer. As a microtubule inhibitor, cabazitaxel differs from docetaxel because it exhibits a much weaker affinity for P-glycoprotein (P-gp), an adenosine triphosphate (ATP)-dependent drug efflux pump. Cancer cells that express P-gp become resistant to taxanes, and the effectiveness of docetaxel can be limited by its high substrate affinity for P-gp. Clinical studies confirmed that cabazitaxel retains activity in docetaxel-resistant tumors. Common adverse events with cabazitaxel include diarrhea and neutropenia. Cabazitaxel in combination with prednisone is an important new treatment option for men with docetaxel-refractory metastatic CRPC (castration-resistant prostate cancer).
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: Avoid with clarithromycin, rifabutin, rifampicin and telithromycin. Antidepressants: Avoid with St John's wort. Antiepileptics: Avoid with carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone. Antifungals: Avoid with itraconazole, ketoconazole and voriconazole. Antipsychotics: Avoid with clozapine (increased risk of agranulocytosis). Antivirals: Avoid with atazanavir, indinavir, ritonavir and saquinavir.

Technology Process of Cabazitaxel

There total 67 articles about Cabazitaxel which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 96.1%

C49H65NO15 → carbazitaxel (183133-96-2,1714967-27-7)

Guidance literature:

With methanol; at 20 ℃; for 2h;

Reference yield: 95.0%

2’-(1-ethoxyethyl)cabazitaxel (1357159-78-4) → carbazitaxel (183133-96-2,1714967-27-7)

Guidance literature:

With hydrogenchloride; In tetrahydrofuran; ethanol; at -8 - 0 ℃; for 23.5h;

Reference yield: 90.0%

(2α,5β,7β,10β,13α)-4-(acetyloxy)-13-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-[2-methoxy-2-prop-2-yl oxy]-3-phenylpropionyl}oxy)-1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxy-11-ene-2-yl benzoate → carbazitaxel (183133-96-2,1714967-27-7)

Guidance literature:

With hydrogenchloride; In tetrahydrofuran; water; at 20 - 25 ℃; for 3h;

upstream raw materials:

10-deacetylbaccatin III

1-hydroxy-7β,10β-di-methoxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-trethylsilyloxy-3-phenylpropanoate}

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene

tert-butyl (3R,4S)-2-oxo-4-phenyl-3-(triethylsilyloxy)azetidine-1-carboxylate

Downstream raw materials:

(αR, βS)-α-hydroxy-β-[[(1,1-dimethylethoxy)carbonyl]amino]benzene-propanoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,1112,12a,12b-dodecahydro-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester isopropanol solvate

Refernces

• 1、 -. "Preparation method of cabazitaxel". . . Retrieved 2021/11/27.
• 2、 -. "Method for synthesizing cabazitaxel by using 10-deacetylbaccatin III". . . Retrieved 2018/06/23.