• 2010 New Drug Approvals - Pt. VI - Polidocanol (Asclera)




    ATC code: C05BB02

    On March 30th, the FDA approved Polidocanol under the trade name Asclera. Polidocanol is a sclerosing agent indicated to treat uncomplicated spider veins (varicose veins ≤1 mm in diameter) and uncomplicated reticular veins (varicose veins 1 to 3 mm in diameter) in the lower extremities. Varicose veins develop when the small valves inside the veins no longer work properly, allowing the blood to flow backwards and then pool in the vein.
    When injected intravenously, Polidocanol works by locally damaging the endothelium of the blood vessel, causing platelets to aggregate at the site of damage and attach to the venous wall. Eventually, a dense network of platelets, cellular debris and fibrin occludes the vessel, which is then replaced with connective fibrous tissue. As one would expect for this type of molecule and also the mechanism of action, there is believed to be no specific molecular target for Polidocanol.
    Polidocanol is a large 'small molecule' drug (Molecular Weight of 583 g.mol-1), with a mean half-life of 1.5 hr. Polidocanol is administrated intravenously and the strength of the solution and the volume injected depend on the size and extent of the varicose veins. Thus, the recommended dosage is 0.1 to 0.3 mL for each injection (Asclera 0.5% for spider veins and Asclera 1% for reticular veins) into each varicose vein, and a maximum recommended volume per treatment session of 10 mL.
    Polidocanol's chemical structure is 2-[2-[2-[2-[2-[2-[2-[2-[2-(dodecyloxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol. It is a non-ionic detergent, similar to polyethylene glycol (PEG) in structure, consisting of two components, a polar hydrophilic (dodecyl alcohol) and an apolar hydrophobic (polyethylene oxide - the part in brackets in the chemical structure) chain. 
    NAME="Polidocanol"
TRADEMARK_NAME="Asclera"
ATC_code="C05BB02"
SMILES="CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO"
InChI="InChI=1S/C30H62O10/c1-2-3-4-5-6-7-8-9-10-11-13-32-15-17-34-19-21-36-23-25-38-27-29-40-30-28-39-26-24-37-22-20-35-18-16-33-14-12-31/h31H,2-30H2,1H3"
InChIKey="ONJQDTZCDSESIW-UHFFFAOYSA-N"
ChemDraw=Polidocanol.cdx


    The license holder is Chemische Fabrik Kreussler & Co. and the product website is www.asclera.com.
    
	  
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    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.
    
	  
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    ChEMBL on BioTorrents
    
	  	
	  	
    

We have uploaded 2 torrent files on to the BioTorrents website, one contains the chembl_04 flat files the other the chembl_04 mysql database. You can access the files here.


    

    

More information about BioTorrents file sharing service can be found here.


    

    

Thanks to Morgan Langille for setting up the service and answering a number of questions I had during upload process.
    
	  
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    Free Poster on Human Oral Drug Targets
    
	  	
	  	
    We have a number of posters available associated with the NRDD review 'How many drug targets are there?" available; if you would like one or two of these, please mail us
    
	  
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    ChEMBL Assays are now in PubChem....
    
	  	
	  	
    The assays from ChEMBL are now in PubChem! - click here for a view.
    
	  
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    ChEMBL_04 downloads now available
    
	  	
	  	
      We are pleased to announce the release of the latest version of the ChEMBL database: chembl_04  
    

    
In addition to the inclusion of new data from the primary scientific literature, three neglected-disease datasets have been deposited in the database: Plasmodium falciparum screening data from GSK, Novartis/GNF and St Jude Children's Research Hospital. These datasets can be identified on the basis of their src_id in the compound_records and assays tables. For more information, or to download the full deposited datasets, please visit the new ChEMBL-NTD website: https://www.ebi.ac.uk/chemblntd  
    

    
You can access the data via the ChEMBL database interface: https://www.ebi.ac.uk/chembldb/index.php  
    

    
Alternatively you can download the ChEMBL database (Oracle 9i, 10g, 11g, or MySQL) from our ftp site: ftp://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/latest/  
    

    
For details of upcoming webinars, please see: https://chembl.blogspot.com/search/label/Webinar
    
	  
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    4th Annual Forum for SMEs - October 18th-19th, Munich
    
	  	
	  	
    The 4th Annual Forum for SMEs is being held in Munich on October the 18th-19th 2010. The meeting has the aim of showcasing the facilities and support offered by EMBL-EBI for Small and Medium Enterprises (SMEs). The meeting also has a series of sessions from the European Patent Office (EPO).
    

    Further details can be found on the ENFIN website
    
	  
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    ChEMBL-NTD Interface Walkthrough - Thursday 24th June, 3pm BST
    
	  	
	  	

    
We are running a brief web-based walkthrough of the ChEMBL-NTD deposited data and interface on Thursday 24th June 2010 at 3pm BST. If you are interested in receiving links to the meeting and a telephone number to call, please mail us. (Please, please, please use this link to mail, otherwise things easily get lost).
    
	  
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