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Cambridge MedChem Consulting

Gates Foundation insists on open access publishing

The Gates foundation's policy on open access publishing became enforced from Jan 1st 2017 and so all research from Gates funded projects can only by published in Open Access journals.

The details of the policy are available online

In particular

  • Publications Are Discoverable and Accessible Online. Publications will be deposited in a specified repository(s) with proper tagging of metadata.

  • Publication Will Be On “Open Access” Terms. All publications shall be published under the Creative Commons Attribution 4.0 Generic License (CC BY 4.0) or an equivalent license. This will permit all users of the publication to copy and redistribute the material in any medium or format and transform and build upon the material, including for any purpose (including commercial) without further permission or fees being required.

The NIH insists that publications must be made freely available 12 months after publication, Wellcome Trust, also mandates OA publishing, but its policy permits a six-month embargo on making published papers open. CRUK currently encourage, and where an article processing charge is paid, require, license research papers using the Creative Commons Attribution licence (CC-BY). The research councils in the UK have also committed to Open Access publishing as do DNDI.

With charitable funding playing an increasingly important role in drug discovery complying with these Open Access requirements is likely to have a significant impact on the publication landscape.

The SULSA Assay Development Fund:

I've worked with a couple of academic groups who have a very interesting target but no small molecule leads. Whilst there are several places offering high-throughput screening the stumbling block is often development of a robust screening assay running in a high density format. Most academic groups have little experience in developing such an assay and to be honest will need to do so very infrequently.

The SULSA Assay Development Fund: accelerating translation of new biology from academia to pharma DOI describes efforts to support the development of such assays, work carried out in collaboration with the European Lead Factory in Newhouse.

However, many scientifically interesting, novel molecular targets lack associated high-quality, robust assays suitable for hit finding and development. To bridge this gap, the Scottish Universities Life Sciences Alliance (SULSA) established a fund to develop assays to meet quality criteria such as those of the European Lead Factory. A diverse project portfolio was quickly assembled, and a review of the learnings and successful outcomes showed this fund as a new highly cost-effective model for leveraging significant follow-on resources, training early-career scientists and establishing a culture of translational drug discovery in the academic community.

European Lead Factory technical acceptance criteria

  • Minimally 384 wells (max 30 μl)
  • Homogenous assay (no washing steps)
  • Defined endpoint
  • Z-prime >0.6
  • Readout stability >1 h
  • S/B signal >3
  • Incubation times <4 h
  • DMSO tolerance: minimum 0.5%
  • All reagents minimally 8 h stable
  • Recombinant proteins(s) >80% pure

Perhaps this quote sums things up very nicely.

‘We only got so far in optimising our assay because in my opinion we do not have either the equipment or the personnel with the skill set required to do this efficiently. So being able to come and work at Newhouse where you are then surrounded by people who can identify quickly where assay improvements should be made and then pass on the knowledge of how to set about applying these changes (as well as gaining experience with various pieces of equipment) was invaluable.’

More details are available here http://www.sulsa.ac.uk/sites/sbsweb2.bio.ed.ac.uk.sulsa/files/downloads/SULSAassaydevelopmentfundguidancenotes4.pdf

The Wellcome Trust also provides Seed/Pathfinder awards that could cover similar projects.

Annual Site review

As 2016 ends I'd like to take the chance to wish you all a Happy New Year and hope for great success in your drug discovery endeavours.

This website continues to increase in popularity with over 108,000 page views, an increase of 16% over the figure for 2015. The pages were visited by over 50,000 viewers and around a quarter of the visitors come back on multiple occasions suggesting they find it useful. The visitors come from 160 different countries with the US and UK topping the list.

The most viewed pages were

Interestingly the Books and Grant funding research have seasonal peaks in viewing.

Looking at the operating systems 57% are Windows users, 22% Mac users, 10% iOS and 8% Android, Chrome dominates the browser stats (58%) with Safari second (20%) and Firefox third (15%).

Seasons Greetings

MerryChristmas

As in previous years all monies saved for not sending greetings cards will be given to the Multiple Sclerosis Society

Published Fragments Page Updated

I've just updated the published fragments page.

pubfrags

Another European Lead Factory success

We are now starting to see some of the results of the screening of academic projects at the European Lead factory that was initiated in 2013.

Dr Mahlapuu’s group, based at the University of Gothenburg, first identified a new target which could be used to reverse metabolic complications in type 2 diabetes. With the help of the European Lead Factory experts, she then screened the Joint European Compound Library of the then 320,000 industry compounds and identified a set of selective and potent small molecules which interfere with this target.

They have now formed a spinout company to develop these leads. ScandiCure has received 1 MSEK from the 2016 SWElife program to continue the development of first-in-class anti-diabetic drug based on small molecule antagonists of a novel key mediator - serine/threonine protein kinase 25 (STK25).

Updated brain penetration page

I've updated the brain penetration page to include data from a recent publication, Small Molecule Kinase Inhibitors for the Treatment of Brain Cancer DOI which discusses the issues with targeting brain and central nervous system cancers.

macrolisation

Nucleic Acid Research Database Issue

I've just been browsing through the NAR Database issue whilst the the historical focus was on molecular biology resources the current issue contains over 500 resources that would be of interest to drug discovery. In addition to well known databases like ChEMBL, PubChem BioAssay and RCSB there are many others. A few that caught my eye:

TransportersDB Database of membrane transporters
SureChEMBL Annotated patent database
canSAR Cancer research and drug discovery knowledgebase
iPPI-DB Modulators of protein-protein interactions
Withdrawn Withdrawn drugs
Open Targets platform for therapeutic target identification and validation

ELF and antibiotic resistance programme

The latest news report from the European Lead Factory highlights work targeting antimicrobial resistance in collaboration with Professor Chris Schofield (University of Oxford). The high throughput screen of >300,000 compounds and initial triaging provided 50 qualified hits.

Multiple series of compounds were validated through resynthesis, biochemical and biophysical profiling at the European Screening Centre site in Newhouse, complemented with ligand–protein crystallography and antimicrobial evaluation at University of Oxford

Great to see projects like this move forward, demonstrates how important the ELF is in providing hits for academic groups/small companies.

Predicting Sites of Metabolism page updated

I've updated the Predicting sites of metabolism page.