2010 New Drug Approvals - part VIII - Cabazitaxel (Jevtana)

ATC code (partial): L01CD

The FDA approved Cabazitaxel on June 17th. Cabitaxel is used in combination with prednisone to treat advanced, hormone-refractory prostate cancer.

Typically, prostate cancer occurs in older males and is among the most common forms of cancer affecting men with around 200,000 new cases per year diagnosed in the United States. Prostate cancer is a glandular cancer that is generally slow-growing. However, prostate cancer develops the ability to penetrate into other tissues and to form metastases.

Cabazitaxel is a new antineoplastic agent that inhibits the function of microtubules. Like other taxanes, it binds to beta-tubulin and promotes and maintains its incorporation in the assembled microtubule. As a consequence the dynamic structure of the microtubule cytoskeleton is 'frozen' and the concentration of free tubulin decreased. Mitotic cells, which depend on microtubules to restructure their shape and organelle organization, undergo apoptosis or stop progressing through the cell cycle. Thus, tumor growth is stalled.

Chemically, cabazitaxel is a dimethylated variant of the state-of-the-art treatment docetaxel. Cabazitaxel is an example of a semin-synthetic natural product, with the key raw ingredient isolated from yew leaves. Cabazitaxel is a lipophillic molecule with a high molecular weight 835.93 g.mol-1).
The volume of distribution (Vss) is 4,864 L. In vitro, the binding of cabazitaxel to human serum proteins was 89 to 92%. Cabazitaxel is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL). Cabazitaxel is extensively metabolized in the liver (> 95%), mainly by the CYP3A4/5 isoenzyme, and to a lower extent by CYP2C8. Clearance (primarily as metabolites) is via both urine and feces. Cabazitaxel has a plasma clearance of 48.5 L.hr-1.
Clinical trials with showed a statistically significant increase in survival rate by 2.4 month.
Cabazitaxel is to be administered as an intravenous infusion of 25mg/mm²(body surface) every three weeks in combination with a daily regiment of 10mg prednisone.
Cabazitaxel comes with a black box warning (fatal neutropenia). Patients have to be monitored for changes in neutrophil counts and treatment appropriately adjusted if a drop below 1500 neutrophils/mm³ is observed. Other adverse side effects of cabazitaxel are hypersensivity reactions, gastrointestinal symptoms and renal failure.

Cabazitaxel is marketed by Sanofi-Aventis under the name Jevtana. This is a link to the full prescribing information.

SMILES:

CO[C@H]1C[C@H]2OC[C@@]2(OC(C)=O)[C@H]3[C@H](OC(=O)c4ccccc4)[C@]5(O)C

[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)c6ccccc6)C(=C([C@@H](OC)C

(=O)[C@]13C)C5(C)C)C

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

InChI-Key:

BMQGVNUXMIRLCK-OAGWZNDDSA-N

Chemdraw: cabazitaxel.cdx

Comments

ChEMBL 34 is out!

We are delighted to announce the release of ChEMBL 34, which includes a full update to drug and clinical candidate drug data. This version of the database, prepared on 28/03/2024 contains: 2,431,025 compounds (of which 2,409,270 have mol files) 3,106,257 compound records (non-unique compounds) 20,772,701 activities 1,644,390 assays 15,598 targets 89,892 documents Data can be downloaded from the ChEMBL FTP site: https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/ Please see ChEMBL_34 release notes for full details of all changes in this release: https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/chembl_34_release_notes.txt New Data Sources European Medicines Agency (src_id = 66): European Medicines Agency's data correspond to EMA drugs prior to 20 January 2023 (excluding vaccines). 71 out of the 882 newly added EMA drugs are only authorised by EMA, rather than from other regulatory bodies e.g.

New SureChEMBL announcement

(Generated with DALL-E 3 ∙ 30 October 2023 at 1:48 pm) We have some very exciting news to report: the new SureChEMBL is now available! Hooray! What is SureChEMBL, you may ask. Good question! In our portfolio of chemical biology services, alongside our established database of bioactivity data for drug-like molecules ChEMBL , our dictionary of annotated small molecule entities ChEBI , and our compound cross-referencing system UniChem , we also deliver a database of annotated patents! Almost 10 years ago , EMBL-EBI acquired the SureChem system of chemically annotated patents and made this freely accessible in the public domain as SureChEMBL. Since then, our team has continued to maintain and deliver SureChEMBL. However, this has become increasingly challenging due to the complexities of the underlying codebase. We were awarded a Wellcome Trust grant in 2021 to completely overhaul SureChEMBL, with a new UI, backend infrastructure, and new f

Accessing SureChEMBL data in bulk

It is the peak of the summer (at least in this hemisphere) and many of our readers/users will be on holiday, perhaps on an island enjoying the sea. Luckily, for the rest of us there is still the 'sea' of SureChEMBL data that awaits to be enjoyed and explored for hidden 'treasures' (let me know if I pushed this analogy too far). See here and here for a reminder of SureChEMBL is and what it does. This wealth of (big) data can be accessed via the SureChEMBL interface , where users can submit quite sophisticated and granular queries by combining: i) Lucene fields against full-text and bibliographic metadata and ii) advanced structure query features against the annotated compound corpus. Examples of such queries will be the topic of a future post. Once the search results are back, users can browse through and export the chemistry from the patent(s) of interest. In addition to this functionality, we've been receiving user requests for local (behind the

Mapping lists of IDs in ChEMBL

In order to facilitate the mapping of identifiers in ChEMBL, we have developed a new type of search in the ChEMBL Interface. Now, it is possible to enter a list of ChEMBL IDs and see a list of the corresponding entities. Here is an example: 1. Open the ChEMBL Interface , on the main search bar, click on 'Advanced Search': 2. Click on the 'Search by IDs' tab: 3. Select the source entity of the IDs and the destination entity that you want to map to: 4. Enter the identifiers, you can either paste them, or select a file to upload. When you paste IDs, by default it tries to detect the separator. You can also select from a list of separators to force a specific one: Alternatively, you can upload a file, the file can be compressed in GZIP and ZIP formats, this makes the transfer of the file to the ChEMBL servers faster. Examples of the files that can be uploaded to the search by IDs can be found here . 5. Click on the search button: 6. You will be redirected to a search resul

New Drug Approvals - Pt. XVII - Telavancin (Vibativ)

The latest new drug approval, on 11th September 2009 was Telavancin - which was approved for the treatment of adults with complicated skin and skin structure infections (cSSSI) caused by susceptible Gram-positive bacteria , including Staphylococcus aureus , both methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains. Telavancin is also active against Streptococcus pyogenes , Streptococcus agalactiae , Streptococcus anginosus group (includes S. anginosus, S. intermedius and S. constellatus ) and Enterococcus faecalis (vancomycin susceptible isolates only). Telavancin is a semisynthetic derivative of Vancomycin. Vancomycin itself is a natural product drug, isolated originally from soil samples in Borneo, and is produced by controlled fermentation of Amycolatopsis orientalis - a member of the Actinobacteria . Telavancin has a dual mechanism of action, firstly it inhibits bacterial cell wall synthesis by interfering with the polymerization and cross-linking of peptid

The ChEMBL-og

Search This Blog