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RSC Medicinal Chemistry Residential School

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There is less than a week left to save £50 with early bird registration for the RSC Medicinal Chemistry Residential School (21-26 June 2015, Burleigh Court Conference Centre, Loughborough University, UK).

The school is designed for graduate and post-doctoral chemists with 1-5 years' experience in the field of drug research. Drug discovery is an interdisciplinary subject so delegates from biological or computational backgrounds will benefit from attendance at the school. In addition, final year PhD students from pharmaceutical or organic chemistry contemplating a career in drug discovery are also encouraged to attend.

Full details here

Mitigating risk in academic preclinical drug discovery

An interesting paper in Nature Reviews Drug Discovery for those involved in academic drug discovery.

Mitigating risk in academic preclinical drug discovery, Jayme L. Dahlin, James Inglese & Michael A. Walters DOI

Here, we have outlined some risk mitigation strategies that can help set the stage for effective engagement at the academic–applied science interface. However, even with the best risk management, >95% of these projects will fail

The last point is particularly important for PhD student supervisors to note.

Hatfield MedChem Meeting

26th symposium on Medicinal Chemistry in Eastern England (Hatfield symposium)

Thursday, 23rd April 2015 The Fielder Centre, Hatfield, Herts, UK

Speakers and Presentations Identification of orally bioavailable type 2 inhibitors of discoidin domain-containing receptor 1/2 (DDR1/DDR2) using “back-to-front” X-ray FBDD Emiliano Tamanini, Astex Therapeutics

Drug discovery towards the eradication of malaria Paul Willis, Medicines for Malaria Venture

Exploring water networks to predict binding affinity and selectivity Daniel D Robinson, Schrödinger

URAT-1 solute carrier inhibitor program for the treatment of gout Ian Storer, Pfizer

The discovery of potent brain penetrant BACE inhibitors Fionna Martin, Lilly

The monster mas agonist – revealing the beauty in the beast Simon Peace, GlaxoSmithKline

The discovery of therapeutics for neglected diseases and the translation of novel biology through small molecule drug discovery Andrew Woodland, Drug Discovery Unit, University of Dundee

A softdrug approach to PDE4 inhibitors for the topical treatment of skin diseases Nuria Aguilar, Almirall

The European Lead Factory: a pan-European approach to access new chemical space for drug discovery Adam Nelson, University of Leeds

Novel 5-HT7 antagonists, with an unprecedented selectivity profile, for the treatment of migraine Ali Ates, UCB

Sulfoximine substituted morpholino-pyrimidines for the treatment of cancer Kevin Foote, AstraZeneca

Event website www.maggichurchouseevents.co.uk/bmcs

Free Compound Screening for antimicrobial activity

The concerns about antibiotic resistance are well known and indeed have made headlines in the mainstream press. Here is a chance to help find the next generation of antibiotics.

Do you have interesting compounds sitting on the shelf? Perhaps you would be interested in having them screened for antibiotic activity for free?

The Community for Open Antimicrobial Drug Discovery would like to hear from you, their goal is to screen compounds from academic research groups from anywhere in the world for free.

The requirements are pretty minimal

We ask for 1-2 mg of pure compound which will be used for primary screening, hit confirmation, and if active will be used for a broader antimicrobial screening, cytotoxicity and a check for its purity. We require all compounds to be soluble in water or DMSO and to be shipped as dry material in appropriate containers, such as 1-2 mL Eppendorf tubes. For larger collections we can arrange plates or tube-racks.

In the primary screen they test against against key ESKAPE pathogens, E. coli, K. pneumoniae, A. baumannii, P. aeruginosa, S. aureus (MRSA), as well as the fungi C. neoformans and C. albicans. The ‘ESKAPE’ pathogens that are responsible for two-thirds of all health care-associated infections and resistant strains of these bacteria represent the greatest unmet need in antibacterial drug development.

Drug Discovery Resources Updated

I've just completed a couple of updates to the Drug Discovery Resources.

In particular I've updated the page on Frequent Hitters, False Positives, Promiscuous Compounds that are seen in every screening campaign and can waste valuable resources if not flagged early. I've also updated the page on Molecular Interactions expanding the sections on less common interactions such as bonding to sulphur and halogens.

New Compound Sets Identified from High Throughput Phenotypic Screening Against Three Kinetoplastid Parasites: An Open Resource

The GSK high-throughput screening group at Tres Cantos and collaborators have just published DOI the results of whole-cell phenotypic screens against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Three anti-kinetoplastid chemical boxes of ~200 compounds each were assembled. Functional analyses of these compounds suggest a wide array of potential modes of action against kinetoplastid kinases, proteases and cytochromes as well as potential host–pathogen targets. The compound sets are provided as an open resource for the scientific community.

srep08771-f1

Open Source Malaria Project

The Open Source Malaria team have submitted an entry for the Thinkable Open Innovation competition

Here it is: https://www.thinkable.org/submission/2055 Please go and watch the video and vote for the team.

The prize is $5000 and every dollar of the prize would go to supporting malaria research in OSM.

So please go to https://www.thinkable.org/submission/2055, sign up to Thinkable (very quick and easy - you can sign in through Facebook etc if you like) and vote for the project and tell your friends.

Putting a spotlight on University Technology Transfer

If you are an academic involved in drug discovery there is a paper in Nature Biotechnology that you should read that tells you what you need to know about your technology transfer office (TTO) doi.

The administrative complexity and opacity in university technology transfer presents an extra obstacle to academic entrepreneurs who already face a multitude of technical and commercial hurdles before their discovery can reach the marketplace. The best way to overcome these issues is to be fully informed before initiating negotiations with your TTO. We hope the information in this article will better prepare you to meet these challenges.

The article gives information on how long the negotiations can take with the TTO (up to 18 months!), and what you can do to improve the process. There is also the issue of the size of the stake the university will claim in the fledgling company

Perhaps the most striking difference between the United States and United Kingdom is seen with equity deal terms. In the United Kingdom, a typical licensing deal is a rarely negotiable 50:50 split between the university and the academic bioentrepreneur, whereas US interviewees often reported universities taking a 5–10% negotiable equity share.

The authors have tried to gather together the IP policies of the major universities in the US and UK and tabulated the equity share taken, some universities take 5% whilst others take over 67%. It should also be noted that in addition to the initial equity stake there might be long term milestone payments that need to be factored into the equation.

At a time when there is an effort to increase academic involvement in early stage drug discovery it is useful to have the spotlight shone on this often opaque area. Whilst this paper only reviews US and UK institutions I suspect similar issues exist in other countries.

Fragments in the clinic

The acid test for any new technology in drug discovery is whether it translates into drugs in the clinic. Practical Fragments have been keeping a track on candidates discovered using fragment-based screening and the 2015 update now contains over 30 drugs in various stages of clinical development. As someone who has seen a number of technologies come and go I'm delighted to see that fragment-based approaches are delivering where it counts.

There is more information on fragment-based screening in the Drug Discovery Resources.

18th SCI/RSC Medicinal Chemistry Symposium

The second flyer for the 18th SCI/RSC Medicinal Chemistry Symposium (Sunday 13 - Wednesday 16 September 2015 Churchill College, Cambridge , UK) is now available.

Again we have an outstanding international lineup with a special focus on challenging targets, "Drugging the undruggable".

The flyer including the application form can be downloaded from here.