The ChEMBL-og

I put together a graph this afternoon, from home, with no real network connection, no database access and a sick dog - so treat the rendering of the data as preliminary, but I think it is quite interesting. Anyway, below is a retrospective view of 2008 US drug approvals. 10 Orals, 13 Parenterals and 1 Topical. 2 Natural Product derived drugs (excluding peptide drugs). All is well with the Rule of Five. 6 with black-box warnings. 1 new target (but quite a few with unknown mode of action). 20 small molecules, and 4 peptide/protein drugs.....

Next in our series of posts on new FDA drug approvals this year is Canakinumab, approved on the 18th of June. Canakinumab is a Interleukin-1 beta (IL-1β) blocker indicated for the treatment of various auto-immune diseases - specifically described by the term Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) (alternatively known as familial cold urticaria ) and Muckle-Wells Syndrome (MWS) . These are rare (albeit debilitating) genetic diseases, and are usually caused by mutations in the NLRP-3 gene - here is the link to the OMIM entry for NLRP-3. Canakinumab is the third Il-1β blocker to reach the market, and as the INN/USAN suggests it is a human (the 'u' before mab) derived monoclonal antibody (the 'mab' part). The earlier IL-1β blockers were Anakinra (Kineret), and Rilonacept (Arcalyst); both of these earlier therapies are not antibody therapies, and have different detailed mechanisms of action. Canakinumab bi...

To make things a little simpler, and to allow rapid visual comparisons, we have set up a series of icons for our New Drug Approvals posts. These are very simple, and should be self explanatory. Three examples should make everything clear. A small molecule, Rule-of-Five compliant, oral drug A large molecule, parenteral drug, against a new target, with a black box warning. A natural product-derived topical drug Well maybe things are not as clear as could be..... but hey, you guys and gals are smart, and will soon work it out; and I am sure the magic blog pixies will add the correct icons to the previous posts.

To jpo and Bissan a son - Albert Mohio. Normal service will be resumed as soon as possible.

Artemether: Lumefantrine: Next in our series of posts on 2009 new drug approvals is a mixture of Artemether (USAN) - a methyl ether derivative of artemisinin, and Lumefantrine (USAN) - a racemic mixture of a synthetic racemic fluorene derivative formerly known as benflumetol. The combination of these two drugs in one product was approved on April 7th. The mixture is marketed under the trade name Coartem, for the treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum , the causative parasite of the most aggressive form of the disease. Artemether and Lumefantrine are both small molecule drugs (molecular weights of 298.4 g.mol-1 and 528.9 g.mol-1, respectively), lipophilic, and are both essentially insoluble in water. Artemether is fully Rule-of-Five compliant, whereas Lumefantrine is not. Artemether and Lumefantrine have increased oral absorption when administrated with food and display high plasma protein binding of 95.4% and 99.7%, respectively. Arteme...

Also approved this year, on March 30th 2009, is Everolimus (USAN). Everolimus is an inhibitor of mTOR ( mammalian target of rapamycin ), a serine-threonine kinase, and is indicated for the treatment of advanced renal cell carcinoma after failure of treatment with Sunitinib or Sorafenib. Sunitinib and Sorafenib are both orally dosed small molecule inhibitors of protein kinases. Everolimus is also marketed under the trade name (although not currently in the US) as Certican, which is used for immunosuppression in transplant therapy. Everolimus (previously known by the research code RAD-001) is a relatively large 'small molecule' drug (Molecular Weight of 958.2 g.mol-1), lipophilic, orally absorbed and has a low plasma binding of ~74%. Everolimus is primarily metabolized CYP3A4 routes, with known metabolites being essentially inactive as mTor inhibitors, these are largely excreted in the feces. Everolimus has a long mean elimination half-life of ~30 hours. Typical dosage is 10 mg ...

We are going to speak at the forthcoming MipTec meeting in Basel - this is a free registration meeting, so it is pretty unusual (and good!). We will speak on bioisostere discovery from our chEMBL databases - probably in the area of peptide drugs and peptide bioisosteres. The meeting website is here .... As you may have noticed, today is a catch up with things-to-do-day, and also we are celebrating some of the kings (and maybe later, queens) of british comedy in the the blog pictures.