As someone who regularly reads Derek Lowe’s “In the Pipeline” blog I was taken with the post on The Smallest Drugs in which he highlighted the structures using the arbitrary cutoffs
the molecular weight cutoff was set, arbitrarily, at aspirin's 180. I excluded the inhaled anaesthetics, only allowing things that are oils or solids in their form of use. As a small-molecule organic chemist, I only allowed organic compounds - lithium and so on are for another category.
An interesting selection but I thought it might be interesting to profile the calculated properties, I used the DrugBank Database too ensure I got a more comprehensive dataset and then calculated properties as I have done for the Fragment collections. The results are shown below. Probably the most notable feature is the number that contain ionisable groups, over 60% of the molecules would be predicted to be ionised at physiological pH (note however it does include a couple of natural amino acids). Around 50% contain an aromatic ring (of which 2/3 are heterocycles). There are a couple of structures with more 3D shape (Memantine) but in general they would be classified as disc or rod-like. In general the results don’t look too dissimilar to the Published Fragment Hits.
I’ve updated the page on published fragments, the dataset now includes over 800 published fragments hits abstracted from over 200 publications directed at nearly 130 different molecular targets using 22 different detection technologies and might be expected to give some insight into the type of compounds that appear as hits. With the caveat that the dataset only includes information that has been published.
UK researchers will be granted access to a ‘virtual library’ of deprioritised pharmaceutical compounds through a new partnership between the Medical Research Council (MRC) and seven global drug companies, announced today by Business Secretary Vince Cable.
AstraZeneca, GlaxoSmithKline, Janssen Research & Development LLC*, Lilly, Pfizer, Takeda and UCB will each offer up a number of their deprioritised molecules for use in new studies to improve our understanding of a range of diseases. A full list of available compounds will be published later this year, when UK scientists will be able to apply for MRC funding to use them in academic research projects.
This has the potential to a really exciting resource for scientists to explore the pathways involved in a variety of different diseases, and since the compounds have apparently undergone some development it may provide a boon to those involved in repurposing drugs. Much will of course depend on the compounds offered but perhaps other companies will follow suit.
18th SCI/RSC Medicinal Chemistry Symposium Sunday 13 - Wednesday 16 September 2015 Churchill College, Cambridge , UK
Europe’s premier biennial Medicinal Chemistry event, focusing on first disclosures and new strategies in medicinal chemistry. Reflecting current trends in medicinal chemistry and pharmaceutical research, the theme of the conference will be ‘Drugging the Undruggable’.
A number of conference places will be reserved for poster presenters and contributions are invited from the whole field of medicinal chemistry. Those presenting a poster may also elect to advertise their poster via oral presentation of a single slide ‘flash’ poster. In addition to traditional plenary talks the organising committee wishes to solicit short talks (20 minutes) describing highly impactful but possibly less complete episodes of medicinal chemistry.
Further Information SCI Conference Dept, 14/15 Belgrave Square, London, SW1X 8PS T: + 44 (0)20 7598 1561 E: firstname.lastname@example.org W: www.soci.org
In 1714 the British government threw down the gauntlet to solve the greatest scientific challenge of the century – how to pinpoint a ship’s location at sea by knowing its longitude. Three hundred years later the Longitude Prize 2014 is a challenge with a £10 million prize fund to help solve one of the greatest issues of our time. It is being run and developed by Nesta, with the Technology Strategy Board as launch funding partner.
There are six potential areas highlighted all very worthy causes, however there can only be one prize winner and this is your chance to vote for your preferred project.
WATER How can we ensure everyone can have access to safe and clean water? Water is becoming an increasingly scarce resource. 44 per cent of the world’s population and 28 per cent of the world’s agriculture are in regions of the world where water is scarce. The challenge is to alleviate the growing pressure on the planet’s fresh water by creating a cheap, environmentally sustainable desalination technology.
ANTIBIOTICS How can we prevent the rise of resistance to antibiotics? The development of antibiotics has added an average of 20 years to our life. Yet the rise of antimicrobial resistance is threatening to make them ineffective. This poses a significant future risk as common infections become untreatable. The challenge is to create a cost-effective, accurate, rapid, and easy-to-use test for bacterial infections that will allow health professionals worldwide to administer the right antibiotics at the right time.
DEMENTIA How can we help people with dementia live independently for longer? It is estimated that 135 million people worldwide will have dementia by 2050, which will mean a greater personal and financial cost to society. With no existing cure, there is a need to find ways to support a person’s dignity, physical and emotional wellbeing. The challenge is to develop intelligent, affordable integrated technologies that revolutionise care for people with dementia, enabling them to live independent lives.
FLIGHT How can we fly without damaging the environment? If aircraft carbon emissions continue to rise they could contribute up to 15 per cent of global warming from human activities within 50 years. This needs to be addressed in order to slow down climate change and its detrimental effects on the planet. The challenge is to design and build an aeroplane that is as close to zero-carbon as possible and capable of flying from London to Edinburgh, at comparable speed to today’s aircraft.
FOOD How can we ensure everyone has nutritious, sustainable food? One in eight people worldwide do not get enough food to live a healthy and fulfilled life. With a growing population and limited resources, providing everybody with nutritious, sustainable food is one of the biggest global problems ever faced. The challenge is to invent the next big food innovation, helping to ensure a future where everyone has enough nutritious, affordable and environmentally sustainable food.
PARALYSIS How can we restore movement to those with paralysis? In the UK, a person is paralysed every eight hours. Paralysis can emerge from a number of different injuries, conditions and disorders and the effects can be devastating. Every day can be demanding when mobility, bowel control, sexual function and respiration are lost or impaired. The challenge is to invent a solution that gives paralysed people close to the same freedom of movement that most of us enjoy. Find out more & vote
The a third edition of the popular book, The Organic Chemistry of Drug Design and Drug Action by Silverman and Holladay has just been released, I’ve added it to the book list.
Vortex users might be interested in a new script that implements an interesting paper from Wagner et al Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach To Enable Alignment of Druglike Properties DOI that describes an algorithm to score compounds with respect to CNS penetration.
Lilly MedChem rules can now be installed using Homebrew. In late 2012 Robert Bruns and Ian Watson published a paper entitled Rules for Identifying Potentially Reactive or Promiscuous Compounds DOI. This article describes a set of 275 rules, developed over an 18-year period, used to identify compounds that may interfere with biological assays, allowing their removal from screening sets.
I’ve made a couple of updates to the Drug Discovery Resources pages. In particular I’ve updated the Published fragments Hits to include more examples, details of “promiscuous” compounds and summary of detection technologies and the targets explored. I’ve also updated the Aspartic Protease inhibitors page.
As ever comments and/or suggestions very welcome.
I spoke at the 25th Symposium on Medicinal Chemistry in Eastern England yesterday and gave a talk/demo on integrating Open Source software into Drug Discovery. I’ve now recorded the demo I showed and put it on YouTube
If you want any further information I’d be happy to try and help.