ChEMBL Resources

Resources:
ChEMBL
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SureChEMBL
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ChEMBL-NTD
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ChEMBL-Malaria
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The SARfaris: GPCR, Kinase, ADME
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UniChem
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DrugEBIlity
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ECBD

Sunday, 20 December 2009

Conference: MGMS Cutting Edge Approaches to Drug Discovery, March 2010


Another good one-day conference next year is the Molecular Graphics and Modelling Society (MGMS) meeting 'Cutting Edge Approaches to Drug Design - 2010' which is held at SOAS on Friday the 12th of March 2010. SOAS is right in the center of London, near to Russell Square tube station, there is loads of cool stuff to do nearby (as well as the talks, of course).

Friday, 18 December 2009

Conference: EMBO/EMBL Chemical Biology 2010


A heads up for a conference on Chemical Biology in September 2010 at EMBL headquarters in the charming German city of Heidelberg. The dates are 22-25 September, and more details will shortly be available on the www.embl.de/conferences website. However, much like TACBAC 2010, we anticipate substantial interest in the conference, so I thought I'd highlight the conference early for you so you could mark your brand new 2010 diaries.

Happy Holidays from all in the ChEMBL team!




It is snowing here in the south-east corner of the United Kingdom, and the traditional winter holidays are almost here, so here is our card, from us, to you, with all our best wishes and thoughts.

Thursday, 17 December 2009

Postdoctoral Position in Computational Chemical Biology/Chemogenomics, ICR


There is a position available that may be of interest to readers of the blog, it is in the lab of one of our close collaborators; the position is a Post-doctoral Training Fellow - Section of Cancer Therapeutics of the Institute of Cancer Research, based in Sutton, Surrey. find here the link to the advert, the deadline for applications in 15th January 2010.

The internet is a wierd place, especially at Christmas, look at that picture - a steak cake (alliterative rhyming food names, cool).

Monday, 7 December 2009

New FDA Approved NMEs of 2009 (so far)



A brief note, really just a picture of a table of the New Molecular Entities of 2009 - there will undoubtedly be a few more approved this year, but this is the story so far.

24 New NMEs; of which 5 are biologicals, 5 are Natural Product derived, 14 are synthetic small molecules. 12 of the drugs have a black box warning at launch. 13 of the NMEs are orally dosed, and 13 pass the Rule of Five.

Now back to thinking about EU grants.....

New Drug Approvals - Pt. XXIII - Ecallantide (Kalbitor)





The first approval of the last month of 2009 is Ecallantide (trade name Kalbitor), approved on December 1st. Ecallantide, previously known by the research code DX-88, is a human plasma kallikrein (P03952) inhibitor indicated for treatment of acute attacks of Hereditary Angioedema (HAE) in patients 16 years of age or older. HAE is a rare genetic disorder, giving the carrier low levels of C1-esterase inhibitor (C1-INH) activity and inherited as an autosomal dominant trait.

C1-INH is the major endogenous inhibitor of plasma kallikrein, and functions to regulate activation of the complement system and also the intrinsic coagulation (or 'contact system' pathway). One critical aspect of this system is the conversion of High Molecular Weight kininogen (HMWk) to the nona-peptide bradykinin by the trypsin-like serine protease - plasma kallikrein. During HAE attacks, disregulated activity of plasma kallikrein result in excessive bradykinin generation; bradykinin is a potent vasodilator, and this activity is thought to be responsible for the characteristic HAE symptoms of localized swelling, inflammation and pain.

Ecallantide has a block box warning (risk of anaphylaxis).

Ecallantide is a potent, selective, reversible inhibitor of plasma kallikrein (Ki of 25pM), which binds to the active site and blocks further access of substrates. Ecallantide is the first subcutaneous treatment approved in the U.S.A. The other available treatment involves the intravenous administration of C1-INH itself. Ecallantide is a polypeptide of 60 aminoacids (Molecular Weight 7054 Da), with a volume of distribution of 26.4L, a plasma clearance of 153 mL/min and an elimination half-life of ~2 hours. The recommended dose is 30 mg, administered subcutaneously as three 10 mg doses (each in 1 mL) injections (the typical dosage is therefore 0.43umol).

Ecallantide is a synthetic peptide, related to region 20-79 of the natural gene Tissue Factor Pathway Inhibitor (P10646), and contain 3 internal disulphide bonds.

Ecallantide sequence: EAMHSFCAFKADDGPCRAAHPRWFFNIFTRQCEEFIYGGCEGNQNRFESLEECKKMCTRD
Ecallanetide target sequence: GCLTQLYENAFFRGGDVASMYTPNAQYCQMRCTFHPRCLLF 
SFLPASSINDMEKRFGCFLKDSVTGTLPKVHRTGAVSGHSLKQCGHQISACHRDIYKGVD 
MRGVNFNVSKVSSVEECQKRCTNNIRCQFFSYATQTFHKAEYRNNCLLKYSPGGTPTAIK 
VLSNVESGFSLKPCALSEIGCHMNIFQHLAFSDVDVARVLTPDAFVCRTICTYHPNCLFF 
TFYTNVWKIESQRNVCLLKTSESGTPSSSTPQENTISGYSLLTCKRTLPEPCHSKIYPGV 
DFGGEELNVTFVKGVNVCQETCTKMIRCQFFTYSLLPEDCKEEKCKCFLRLSMDGSPTRI 
AYGTQGSSGYSLRLCNTGDNSVCTTKTSTRIVGGTNSSWGEWPWQVSLQVKLTAQRHLCG 
GSLIGHQWVLTAAHCFDGLPLQDVWRIYSGILNLSDITKDTPFSQIKEIIIHQNYKVSEG 
NHDIALIKLQAPLNYTEFQKPICLPSKGDTSTIYTNCWVTGWGFSKEKGEIQNILQKVNI 
PLVTNEECQKRYQDYKITQRMVCAGYKEGGKDACKGDSGGPLVCKHNGMWRLVGITSWGE 
GCARREQPGVYTKVAEYMDWILEKTQSSDGKAQMQSPA 
The full prescribing information can be found here.

The license holder is Dyax Corp. and the product website is www.kalbitor.com.