• ChEMBL Molecular Interactions



    ChEMBL small molecule-protein interactions are now available in PSI-MI TAB and XML formats, thanks to the     Proteomics Services group. This dataset includes ChEMBL interactions identified via binding assays with IC50/Ki/EC50/Kd values below 10uM - just under 500,000 interactions in total (with negative/weaker interactions also included in the XML export).

    The data can be accessed via the     PSICQUIC project (Proteomics Standards Initiative Common QUery InterfaCe), which provides programmatic access to a wide range of molecular interaction databases via SOAP and REST web services. For example, this URL retrieves all ChEMBL interactions relating to imatinib (Gleevec).

    Mail us     if you need more info.

  • ようこそ、ケンブルへ！ - Welcome to 剣舞瑠 ! -



    The following is written in Japanese....
    ケンブルチーム(ChEMBL Team)は、欧州バイオインフォマティクス研究所(EMBL-EBI)にあり、創薬研究に有用な化合物やターゲット情報を提供するデータベースを開発しています。

    ChEMBLdbは、創薬研究に有用な医薬品化合物の情報を提供するデータベースです。現在、約50万個の化合物情報、約190万件の活性情報及びそれらのターゲット情報が登録されています。ユーザーは、生物活性化合物の情報を部分構造検索や類似性検索で調査したり、また、ターゲットのアミノ酸配列からBLAST検索でアッセイ情報を収集することができます。

    ケンブルチームでは、キナーゼに特化したカイネースサファリ(Kinase SARfari)のサービスも開始しました。

    日本語でのご質問、ご要望はkaz(at)ebi.ac.ukまでどうぞ。チームメンバー一同、皆さんのご利用をお待ちしています！

  • Conference: Rocky '09





    My kids all think I have a really easy life - international travel, 'holidays' all around the world, and they regularly come out with the line 'hard day at the ice-cream factory?' when I say how busy or stressed at work I am. The latest conference we are presenting at does not help, but why oh why do they never hold the conferences I am invited to in somewhere like the Faroe Islands, where the cod fishing is good.

    Anyway, we are speaking at Rocky '09, an ISCB conference held in Aspen, CO from 10th to 12th December. It looks a really, really interesting conference. Here is a link to the schedule.

  • What does the ChEMBL office look like?



    Well, it looks like the picture above. Kudos to Tim Nugent for the photography and image processing.

  • New Drug Approvals - Pt. XXI - Ofatumumab (Arzerra)




    The latest approval this month, on October 26th, was Ofatumumab (trade name Arzerra). Ofatumumab is a CD20-directed cytolytic monoclonal antibody indicated for the treatment of patients with refractory chronic lymphocytic leukemia (CLL) who have inadequately responded to both Fludarabine and Alemtuzumab. CLL is characterized by an abnormal proliferation of lymphocytes so-called B-cells. B-cells originate in the bone marrow and are involved in fighting infection. In CLL, the DNA of a B-cell is damaged and so it can not produce antibodies in order to fight infection. Moreover, they grow out of control and accumulate in the bone marrow and blood.

    Ofatumumab is an IgG1k human monoclonal antibody which binds specifically to both the small and large extracellular loops of CD20. CD20 is a non-glycosylated phosphoprotein expressed on normal B lymphocytes and on B-cell CLL. Since it is not shed from the cell surface, it allows for antibody binding, and when so, it sends a signal across the membrane to control growth and trigger death of certain tumor cells. The Fab domain of Ofatumumab binds to the CD20 molecule, whereas the Fc domain mediates immune effector functions that result in B-cell lysis.
    Ofatumumab has a molecular weight of ca. 149 kDa. The dosing is typically 12 doses administered as an initial 300mg dose, followed 1 week later by a 2,000mg dose weekly for 7 doses, followed 4 weeks later by a further 2,000 mg every 4 weeks for 4 doses (a 2g dose is equivalent to ca. 134umol). It has a volume of distribution ranging from 1.7 L to 5.1 L and its elimination occurs through both a target-independent route and a B-cell mediated route. Ofatumumab clearance is approximately 0.01 L/hr and mean half-life is ca. 14 days. The recommended dosage and full prescribing information can be found here. 

    <CHEMBL_DRUG>
<DRUG_NAME="Ofatumumab" TRADEMARK_NAME="Arzerra">
<DRUG_TARGET UNIPROT="P11836" TARGET_NAME="CD20">
MTTPRNSVNGTFPAEPMKGPIAMQSGPKPLFRRMSSLVGPTQSFFMRESKTLGAVQIMNG
LFHIALGGLLMIPAGIYAPICVTVWYPLWGGIMYIISGSLLAATEKNSRKCLVKGKMIMN
SLSLFAAISGMILSIMDILNIKISHFLKMESLNFIRAHTPYINIYNCEPANPSEKNSPST
QYCYSIQSLFLGILSVMLIFAFFQELVIAGIVENEWKRTCSRPKSNIVLLSAEEKKEQTI
EIKEEVVGLTETSSQPKNEEDIEIIPIQEEEEEETETNFPEPPQDQESSPIENDSSP
</DRUG_TARGET>
</DRUG>
</CHEMBL_DRUG>
    The license holder is GlaxoSmithKline and the product website is www.arzerra.com.

  • Web seminar on chembldb schema


    We will have a web-meeting walkthrough of the chembldb core schema on Friday 20th November at 3pm GMT. The excellent webhuddle will be used, so if you are interested it may be worth checking this out, setting up an account, checking it works on your machine, in advance of the meeting. Mail us if you want links to the phone number and webhuddle link.

  • Recruitment: Data Integration Position for ChEMBL


    Details for a new position within ChEMBL, available for a three year period, are now listed on the EMBL recruitment website.

    The ChEMBL job is (W/09/087/EBI). Closing date is the 30th November 2009.

    The image above is a visualisation of the continental United States of America, visualised by distance to the nearest McDonald's restaurant. Further details and attribution are in the image itself.

  • New Drug Approvals - Pt. XX - Pazopanib (Votrient)



    Another drug onto the market this month is Pazopanib, marketed as Votrient, which was approved on October 19th. Pazopanib Hydrochloride (previously known as GW-786034-B) is the sixth drug to be approved for kidney cancer, after Sorafenib (trade name Nexavar), Sunitinib (trade name Sutent), Temsirolimus (trade name Torisel), Everolimus (trade name Afinitor) and Bevacizumab (trade name Avastin). Sorafenib and Sunitinib are both orally dosed small molecule inhibitors of tyrosine protein kinases, which interfere with tumor growth by inhibiting angiogenesis as well as tumor cell proliferation; Temsirolimus and Everolimus are specific inhibitors of mTOR (mammalian target of rapamycin), a serine-threonine kinase, which interfere with the synthesis of proteins that regulate proliferation, growth, and survival of tumor cells; Bevacizumab is a monoclonal antibody that recognizes and blocks VEGF, which is a chemical signal that stimulates angiogenesis. Pazopanib is a small-molecule drug (Molecular Weight is 437.5 g.mol-1 for Pazopanib itself and 474.0 g.mol-1 for the HCl salt), fully Rule-of-Five compliant, lipophilic and practically insoluble in aqueous media. It is orally absorbed, has a high plasma protein binding of >99% and is metabolized by CYP3A4 (and therefore has many drug-drug interactions with substrates, inhibitors and inducers of CYP3A4) with minor contribution from CYP1A2 and CYP2C8. Pazopanib has a mean half-life of 30.9 hours and elimination is primarily through feces (>96% of dose). The recommended dosage is 800mg once daily (equivalent to ca 1.8 mmol). Among one of the potential adverse events is the propensity for the compound to increase QT interval. Full prescribing information can be found here. Pazopanib has a boxed warning. The structure 5-[[4-[(2,3-dimethyl-2H-indazol-6­-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide. Pazopanib is largely planar and and mimics the adenine ring of the enzyme cofactor ATP. Of additional note is the presence of an aryl-sulphonamide (in the bottom left of the image) - these are often weakly acidic. 
    <NAME="Pazopanib">
<SMILES="O=S(=O)(N)c1c(ccc(c1)Nc2nccc(n2)N(c4ccc3c(nn(c3C)C)c4)C)C">
<InChI="InChI=1/C21H23N7O2S.ClH/c1-13-5-6-15(11-19(13)31(22,29)30)24-21-23-10-9-20(25-21)27(3)16-7-8-17-14(2)28(4)26-18(17)12-16;/h5-12H,1​-4H3,(H2,22,29,30)(H,23,24,25);1H" >
<InChIKey="MQHIQUBXFFAOMK-UHFFFAOYAU">
<ChemDraw=Pazopanib.cdx>
    The manufacturer of Pazopanib is GlaxoSmithKline and the product website is www.votrient.com.