2010 New Drug Approvals - part VII

2010 New Drug Approvals - part VII - Denosumab (Prolia)

ATC code: M05BX04

On June 2nd, the FDA approved Denosumab (previously known as AMG-162), a human monoclonal antibody against RANK-ligand, for the treatment of postmenopausal osteoporosis (PMO). The ATCC code is M05BX04

Osteoporosis is characterized by reduced bone mineral density and a degradation of the small-scale bone structure, leading to increased risk of bone fracture. Osteoporosis is a common disease, affecting primarily women aged 50 and above and are at high risk of fracturing their lumbar vertebrae, hips, wrists and ribs. Osteoporosis is estimated to cause 2 million fractures annually in the US.

Bones undergo constant remodeling that can be understood as a process of simultaneous deconstruction of bone material by osteoclasts (these are big, mobile cells which derive from a common lineage with macrophages) and formation of mineral bone by osteoblasts. Both processes are in a dynamic equilibrium, and this equilibrium keeps the bone mineral density at a stable level. Reduced levels of estrogen, as encountered in women after entering the menopause, increase the number of osteoclasts and promote their activity of resorbing mineral bone. The resulting loss of mineral bone eventually causes osteoporosis.

The bone remodeling equilibrium is regulated by a network of cytokine signalling molecules in which the RANK-ligand (RANKL, O14788) molecule plays a key role, mediating osteoclast activation through binding of the membrane protein receptor activator of nuclear Factor κB (RANK, Q9Y6Q6). RANKL is a member of the tumor necrosis factor (TNF) family of proteins.

Denosumab exerts its effect through binding to RANKL, and is functionally similar to an endogenous protein, osteoprotegerin, a membrane protein that binds RANKL but does not promote any activating effect.

Denosumab is administered as a subcutaneous (s.c.) injection of 60mg once every 6 months. The half-life of Denosumab in blood serum is 24.5 days. Side effects of Denosumab usage are listed as hypocalcemia, serious infections of the skin, abdomen, urinary tract and ear, dermatologic adverse reactions and osteonecrosis of the jaw.

Denusomab is marketed by Amgen under the name Prolia. The full prescribing information can be found here.

Comments

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

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

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

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.

A python client for accessing ChEMBL web services

Motivation The CheMBL Web Services provide simple reliable programmatic access to the data stored in ChEMBL database. RESTful API approaches are quite easy to master in most languages but still require writing a few lines of code. Additionally, it can be a challenging task to write a nontrivial application using REST without any examples. These factors were the motivation for us to write a small client library for accessing web services from Python. Why Python? We choose this language because Python has become extremely popular (and still growing in use) in scientific applications; there are several Open Source chemical toolkits available in this language, and so the wealth of ChEMBL resources and functionality of those toolkits can be easily combined. Moreover, Python is a very web-friendly language and we wanted to show how easy complex resource acquisition can be expressed in Python. Reinventing the wheel? There are already some libraries providing access to ChEMBL d

The ChEMBL-og

Search This Blog