New Drug Approvals 2014 - Pt. VI - Florbetaben F18 (Neuraceq™)

ATC Code: Unavailable

ChEMBL: CHEMBL1908906

On March 19th the FDA approved Florbetaben F18 (Neuraceq™) as a radioactive diagnostic agent for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid (βA) neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease or other causes of cognitive decline.

Alzheimer's disease is the most common form of dementia, can currently not be cured and is characterised by a progressive disease pattern that usually leads to death. Alzheimer's is predicted to affect 1 in 85 people globally by 2050.

Target(s)
Florbetaben binds with high affinity to βA in brain homogenates and selectively labels βA plaques and cerebral amyloid angiopathy. βA (PDB ; Uniprot P05067) denotes 36-43 length peptides that are believed to be crucially involved in the Alzheimer's disease mechanism. βA aggregates in the brain of Alzheimer's patients and is derived from amyloid precursor protein which is cut by certain enzymes. βA and the resulting plaques are toxic to neurons. Following intravenous administration, Florbetaben F18 crosses the blood brain barrier and shows differential retention in brain regions that contain βA deposits. Differences in signal intensity between brain regions showing specific and non specific Florbetaben F18 uptake form the basis for the image interpretation method.

Florbetaben F18 (CHEMBL1908906; Pubchem : 53257383) is a small molecule drug with a molecular weight of 359.4 Da, an AlogP of 3.75, 12 rotatable bonds, and no rule of 5 violations. Florbetaben F18

is administered intravenously.

Canonical SMILES: CNc1ccc(\C=C\c2ccc(OCCOCCOCCF)cc2)cc1
InChi: InChI=1S/C21H26FNO3/c1-23-20-8-4-18(5-9-20)2-3-19-6-10-21(11-7-19)26-17-16-25-15-14-24-13-12-22/h2-11,23H,12-17H2,1H3/b3-2+

Dosage

The recommended dose of Neuraceq is 300 MBq (8.1 mCi), maximum 30 mcg mass dose, administered as a single

slow intravenous bolus (6 sec/mL) in a total volume of up to 10 mL. PET images should subsequently be acquired approximately 45 - 130 minutes after injection over a period of 15-20 minutes.

Warning / limitations of use

A positive Neuraceq scan does not establish the diagnosis of AD or any other cognitive disorder.

Safety and effectiveness of Neuraceq have not been established for:

Predicting development of dementia or other neurologic conditions;
Monitoring responses to therapies.

Neuraceq, similar to other radiopharmaceuticals, contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer.

Pharmacokinetics

Ten minutes after intravenous bolus injection of 300 MBq of Neuraceq in human volunteers, approximately 6% of the injected radioactivity was distributed to the brain. Florbetaben F 18 plasma concentrations declined by approximately 75% at 20 minutes post-injection, and by approximately 90% at 50 minutes.

Elimination

Florbetaben F18 is mainly eliminated via the hepatobiliary route with a mean half-life of approximately 1 hour.

Metabolism

Forbetaben F18 is metabolized mainly by CYP2J2 and CYP4F2.

License holder

The license holder is Piramal Imaging, the highlights of the prescribing information can be found here.

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 ...

Here's a nice Christmas gift - ChEMBL 35 is out!

Use your well-deserved Christmas holidays to spend time with your loved ones and explore the new release of ChEMBL 35! This fresh release comes with a wealth of new data sets and some new data sources as well. Examples include a total of 14 datasets deposited by by the ASAP ( AI-driven Structure-enabled Antiviral Platform) project, a new NTD data se t by Aberystwyth University on anti-schistosome activity, nine new chemical probe data sets, and seven new data sets for the Chemogenomic library of the EUbOPEN project. We also inlcuded a few new fields that do impr ove the provenance and FAIRness of the data we host in ChEMBL: 1) A CONTACT field has been added to the DOCs table which should contain a contact profile of someone willing to be contacted about details of the dataset (ideally an ORCID ID; up to 3 contacts can be provided). 2) In an effort to provide more detailed information about the source of a deposited dat...

Improved querying for SureChEMBL

Dear SureChEMBL users, Earlier this year we ran a survey to identify what you, the users, would like to see next in SureChEMBL. Thank you for offering your feedback! This gave us the opportunity to have some interesting discussions both internally and externally. While we can't publicly reveal precisely our plans for the coming months (everything will be delivered at the right time), we can at least say that improving the compound structure extraction quality is a priority. Unfortunately, the change won't happen overnight as reprocessing 167 millions patents takes a while. However, the good news is that the new generation of optical chemical structure recognition shows good performance, even for patent images! We hope we can share our results with you soon. So in the meantime, what are we doing? You may have noticed a few changes on the SureChEMBL main page. No more "Beta" flag since we consider the system to be stable enough (it does not mean that you will never ...

Improvements in SureChEMBL's chemistry search and adoption of RDKit

Dear SureChEMBL users, If you frequently rely on our "chemistry search" feature, today brings great news! We’ve recently implemented a major update that makes your search experience faster than ever. What's New? Last week, we upgraded our structure search engine by aligning it with the core code base used in ChEMBL . This update allows SureChEMBL to leverage our FPSim2 Python package , returning results in approximately one second. The similarity search relies on 256-bit RDKit -calculated ECFP4 fingerprints, and a single instance requires approximately 1 GB of RAM to run. SureChEMBL’s FPSim2 file is not currently available for download, but we are considering generating it periodicaly and have created it once for you to try in Google Colab ! For substructure searches, we now also use an RDKit -based solution via SubstructLibrary , which returns results several times faster than our previous implementation. Additionally, structure search results are now sorted by...

ChEMBL brings drug bioactivity data to the Protein Data Bank in Europe

In the quest to develop new drugs, understanding the 3D structure of molecules is crucial. Resources like the Protein Data Bank in Europe (PDBe) and the Cambridge Structural Database (CSD) provide these 3D blueprints for many biological molecules. However, researchers also need to know how these molecules interact with their biological target – their bioactivity. ChEMBL is a treasure trove of bioactivity data for countless drug-like molecules. It tells us how strongly a molecule binds to a target, how it affects a biological process, and even how it might be metabolized. But here's the catch: while ChEMBL provides extensive information on a molecule's activity and cross references to other data sources, it doesn't always tell us if a 3D structure is available for a specific drug-target complex. This can be a roadblock for researchers who need that structural information to design effective drugs. Therefore, connecting ChEMBL data with resources like PDBe and CSD is essen...

The ChEMBL-og

Search This Blog