The ChEMBL-og

ATC Code : L01XE17 Wikipedia : Axitinib On Jan 27th 2012, the FDA approved Axitinib (also known as AG-13736, trade name: Inlyta ), a kinase inhibitor, for the treatment of advanced renal cell carcinoma after failure of a first line systemic treatment. Renal Cell Carcinoma (RCC) is a cancer of the lining of proximal convoluted tubules, the tiny tubes through which the blood is filtered, in the kidney. It is the most common type of kidney cancer in adults and is responsible for 80% of all kidney cancers ( Cancer Research UK ). Over 270,000 new cases of kidney cancers are diagnosed every year and the numbers are on the rise ( CRUK ). Axitinib is a tyrosine kinase inhibitor, inhibiting all subtypes of the Vascular Endothelial Growth Factor Receptor (VEGFR), VEGRF1 (Uniprot: P17948 ; ChEMBL1868 ; canSAR ), VEGFR2 (Uniprot: P35968 ; ChEMBL ; canSAR ) and VEGFR3 (Uniprot: P35916 ; ChEMBL ; canSAR ). VEGFRs are single-pass membrane receptors that have multiple extr...

It's sometimes difficult to trace the approval process for drugs in 'foreign' countries - of course, foreign is relative, but nonetheless as a non-local it is difficult to know where to start. As an example, I tried a number of 'social media' approaches to find out about Chinese Drug non-proprietary naming - Quora, Google+ the ChEMBL-og and LinkedIn - LinkedIn was by far the best in terms of useful leads and information, often from 2nd or 3rd away links. Thanks to all that helped so far. Anyway, here's a website in Japan which contains a definitive list of Japanese Drug Approvals, and which has sections in the English language to help non-Japanese readers/speakers. It's the Pharmaceutical and Medical Devices Agency, Japan, website -  http://www.pmda.go.jp/  with an English version at  http://www.pmda.go.jp/english/ There are convenient, yearly approval summaries, in English -  http://www.pmda.go.jp/english/service/list_s.html Package inserts are...

On Jan 23rd 2012 the FDA approved Ingenol mebutate gel for the topical treatment of actinic keratosis (AK). Ingenol mebutate (trade name: PICATO ®, formally known as PEP-005) is a natural product derived from the euphorbia plant. Actinic, or solar keratosis ( Wikipedia ; NIH ; OMIM ) is a pre-cancerous pigmented lesion on the skin, most commonly occurring in skin that has been frequently exposed to the sun. If left untreated, about 20% of cases transform into Squamous Cell Carcinoma . Ingenol mebutate induces cell death in Actinic Keratosis. The precise targets responsible for the mechanism of action is not known, however, Ingenol derivatives (see e.g. CHEMBL346507 ) have been shown to have anticancer activities. Many of these derivatives have activity on several Protein Kinase C isoforms. Mechanistically Ingenol mebutate causes rapid lesion necrosis and also specific neutrophil-mediated, antibody-dependent cellular cytotoxicity Ingenol mebutate (IUPAC: 2-Butenoic acid, ...

There's a really interesting paper just published in Nature Chemistry - 'Quantifying the chemical beauty of drugs' from the group of Andrew Hopkins up at Dundee. Links to the paper are here , and an associated opinion piece in Nature here . We'll add these descriptors to a future release of ChEMBL .... %T Quantifying the chemical beauty of drugs %A G.R. Bickerton %A G.V. Paolini %A J. Besnard %A S. Muresan %A A.L. Hopkins %J Nature Chemistry %V 4 %P 90–98 %D 2012 %O doi:10.1038/nchem.1243

Registration for the Cutting Edge Approaches to Drug Design (CEADD) 2012 meeting is now open. This meeting, organised by the MGMS , is the latest in a highly successful series of conferences, which have been held in collaboration with the RSC-MMG. The meetings are aimed at those who have an interest in the use of computational chemistry in drug discovery and development. This includes medicinal chemists, as well as structural biologists and cheminformaticians. The emphasis is on interdisciplinarity in drug discovery and also on evolving tools and techniques and their application in understanding biological systems. CEADD2012 will be held on Thursday, 26th April, 2012 , at the School of Oriental and African Studies in Russell Square, London. More details, including the list of speakers and information on how to register, can be found at the conference website ( http://www.mgms.org/CEADD2012/index.html ). Joining the MGMS is even easier than ever, and it's cheap; so go on, ...

ATC code: V03AF09 The first FDA new drug approval of 2012 is Glucarpidase, approved on Jan 17th 2012. Glucarpidase (tradename: Voraxaze ; formerly known as carboxypeptidase-G2 or CPG2) is a carboxypeptidase enzyme indicated for the treatment of toxic plasma methotrexate (MTX) concentrations ( > 1 umol/L) in patients with delayed MTX clearance due to impaired renal function. MTX (ChEMBL: CHEMBL426 ) is an antifolate drug and is one of the most widely used anticancer agents. Unlike other anticancer agents, MTX can be safely administrated over a wide dose range. However, during treatment with high doses of MTX, patients may develop renal dysfunction. Since MTX is primarily cleared by renal excretion, this will lead to toxic levels of MTX. Glucarpidase acts by converting MTX to its inactive metabolites 2,4-diamino-N 10 -methylpteroic acid (DAMPA) and gluta mic acid, providing thus an alternate route of elimination to renal excretion. Glucarpidase (Unipr...

A heads up on a course being held on campus here in early July - the joint EMBL-EBI and Wellcome Trust Resources for Computational Drug Discovery . The speakers are excellent, but check out the early material online for the course here. Based on previous courses, please book early to avoid disappointment ;)

The EMBL-EBI is holding one of its regular Open Days on March 1st 2012 - details are at www.ebi.ac.uk/training/openday . These are always really fun events, and give a great insight into life, careers, and activities at our work. The deadline for registration is February 1st 2012.

Many drugs are small molecules that specifically bind to proteins involved in disease related processes. In this way, drugs modulate the function of a targeted protein and ultimately the process causing the disease. The development of drugs crucially relies on assays that measure the potency of the effect a small molecule exerts on its protein target. We compared the potencies of small molecules measured for human proteins and the corresponding (orthologous) protein in rat. Our results suggest that, after subtraction of statistical noise, most human proteins show equivalent potency for small molecule binding as their orthologs in rats. However, we identified a small number of exceptions to this rule, for example the histamine H3 receptor, a protein of the central nervous system. We also compared the potency of small molecules measured against a human protein and another member of the same protein family. In drug development it is often desired to target a protein selectively over ot...

Welcome back after the holiday break! We have a small informal seminar on campus, on Tuesday 17th January 2011 from Alex Tropsha from UNC , the talk will be titled “Many Challenges and Some Solutions for Modeling Chemical Genomics Data: navigating structure – in vitro – in vivo response data space ". If you are interested in attending from off campus - I will need to register you with security - so mail me . Update: The seminar will be at 2pm in seminar room C202 (shared facilities). (Mail to arrange access for off campus attendees though! Update 2: Please note - we cannot provide online access to the talk. Sorry.