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Cambridge MedChem Consulting

Drug Discovery Resources

Just checking the half-year viewing stats for the Drug Discovery Resources section of the website.

The Drug Discovery Resources pages are intended to act as a resource for scientists undertaking drug discovery, they were initially based on a course I give but have been expanded to give much more detail and to cover subjects not covered in the course.

Over the first six months there were nearly 35,000 users with users on average viewing 2-3 pages. The visitors come from 152 different countries with the US (33%), UK (14%) , India (8%), Germany (3.2%) and Canada (3.1%) topping the list.

The most viewed pages over this period were

Looking at the operating systems 56% are Windows users, 20% Mac users, 10% iOS and 10% Android, Chrome dominates the browser stats (65%) with Safari second (17%) and Firefox third (10%).

Open-access Antimicrobial Screening Database

I just got news of the first public release of CO-ADD screening data

CO-ADD is a non-for-profit initiative led by academics at The University of Queensland. Our goal is to screen compound for antimicrobial activity for academic research groups and generate a public knowledge database for the development of novel agents for the treatment of microbial infections. The knowledge base contains chemical structures and antimicrobial activity data from CO-ADD’s screening, made publicly available by the academic research groups, with more data to be released over time.

The database is available here.

COADdatabase

More on hydrogen bonding interactions

Studies of hydrogen bond strength and directionality are largely based on crystal structures which can be biased by crystal packing forces. In a systematic QM study of a wide range of hydrogen bonding groups by Diogo Santos-Martins, Stefano Forli, 34 donors and 67 acceptors DOI they showed there is no correlation between the strength of the hydrogen bond and directionality.

Results demonstrate that there are very strong HB acceptors (e.g.,DMSO) with nearly isotropic interactions, and weak ones (e.g.,thioacetone) with a sharp directional profile. Similarly, groups can have comparable directional propensity, but be very distant in the strength spectrum (e.g., thioacetone and pyridine).

This work also includes a fabulous sheet in the supplementary information giving details of interaction energies for various groups.

I've updated the molecular interactions page.

Funding Opportunities

The GHIT Fund announces an investment opportunity for the Target Research Platform

The GHIT Fund announces an investment opportunity for the Target Research Platform (TRP) in Partnership with the Wellcome Trust. The TRP investments are intentionally broad in potential scope and focus on new technologies and novel approaches.

TRP investments are intentionally broad in potential scope and focus on new technologies and novel approaches. Proposals must be within the project scope and investment eligibility below in order to be considered. The TRP is currently focused on technologies and approaches that address unmet or priority needs within malaria, tuberculosis, HIV/AIDS and Neglected Tropical Diseases listed in the GHIT Intent to Apply form.

MRC/AstraZeneca Centre for Lead Discovery

The MRC/AstraZeneca Centre for Lead Discovery (CLD) aims to support academic researchers in discovering potential starting points for small molecule therapeutic approaches with a clear line-of-sight to therapeutic use. The MRC/AZ Centre for Lead Discovery will form a unique cornerstone for academic and industrial drug discovery projects by supplying high throughput screening (HTS) infrastructure (NiCoLA-B).

Canada-UK Artificial Intelligence Initiative

The call aims to support innovative and cutting-edge interdisciplinary AI research that encourages the exploration of new interdisciplinary research methodologies, approaches and tools that cuts across at least two of the following research domains:

  • social sciences and humanities;
  • health and biomedical sciences; and
  • natural sciences and engineering (including computational and/or mathematical sciences).

There is also a more comprehensive listing of grant funding here.

Where Drugs Come From: A Comprehensive Look

I was going to highlight this article a while back "Academia and industry: allocating credit for discovery and development of new therapies" DOI but got distracted. However I notice that Derek Lowe has written a commentary that is far more detailed than I could have written on his In the Pipeline Blog.

You can read it here Where Drugs Come From it is well worth spending a little reading, digesting and then sending the link to others.

canSAR BLACK

cansar black v1.1.1 now available - includes improved search, new protein family page, and performance improvements

canSAR is an integrated knowledge-base that brings together multidisciplinary data across biology, chemistry, pharmacology, structural biology, cellular networks and clinical annotations, and applies machine learning approaches to provide drug-discovery useful predictions. canSAR’s goal is to enable cancer translational research and drug discovery through providing this knowledge to researchers from across different disciplines. It provides a single information portal to answer complex multi-disciplinary questions including - among many others: what is known about a protein, in which cancers is it expressed or mutated and what chemical tools and cell line models can be used to experimentally probe its activity? What is known about a drug, its cellular sensitivity profile and what proteins is it known to bind that may explain unusual bioactivity?

Open Targets Platform: release 19.06 is out

The latest update of the Open Targets Platform, release 19.06 is available.

This update includes

Target safety information

As a follow-up to the safety data in Open Targets Platform release 19.04, now has more targets with known safety effects and safety risk information, including TBXA2R and JAK2.

TEPs and chemical probes

In this release, they've included the latest Target Enabling Packages (TEPs) for GALT, GALK1 and MLLT1. Also added more chemical probes, small-molecule modulators of a protein’s function that can be used in cell-based or animal studies.

Target-disease associations

A new release always means new evidence available for novel target-disease associations.

Early career MedChem workshop

The Early Career MedChem Workshop is a pre-meeting workshop taking place on the Sunday afternoon before the 20th SCI/RSC Medicinal Chemistry Symposium, Churchill College, Cambridge, Sunday 8 - Wednesday 11 September 2019.

It is aimed at early career (up to 5 years’ experience) medicinal chemists. Registration for this event will be at no additional cost to the main meeting.

The workshop will consist of a team-based exercise around a virtual medicinal chemistry programme and will offer participants:

  • Training in advanced medicinal chemistry
  • Testing out leadership/decision making skills
  • Networking between potential future leaders of different organisations
  • Introductions of possible future collaborators from pharma, CRO, charity and SME sectors
  • Opportunity for informal interaction with experienced medicinal chemists workshop facilitators who will be open to questions around their own experiences
  • Attendance at the full 20th SCI/RSC Medicinal Chemistry Symposium including lectures on a full range of drug targets, key enabling processes and technologies

Feedback from previous events has been excellent for this unique learning experience.

Also note there are student bursaries to help fund attendance at this event, email conferences@soci.org for more information.

Upcoming Conferences

I just thought I'd mention a couple of meetings I'm helping to organise.

2nd RSC-BMCS / RSC-CICAG Artificial Intelligence in Chemistry

Artificial Intelligence is presently experiencing a renaissance in development of new methods and practical applications to ongoing challenges in Chemistry. Following the success of the inaugural “Artificial Intelligence in Chemistry” meeting in 2018 a second meeting has been organised at Fitzwilliam College, Cambridge (2nd to 3rd September 2019). The lineup is now finalised and looks like a great selection of speakers. There is still time to submit posters (closing date 5th July).

AI-webpage-image

Registration is open and there are discounts for RSC members.

The Twitter hashtag - #AIChem19 is already being actively used.

20th SCI/RSC Medicinal Chemistry Symposium

This is Europe’s premier biennial Medicinal Chemistry event, focussing on first disclosures and new strategies in Medicinal Chemistry. It takes place a Churchill College, Cambridge UK, 8 September - 11 September 2019. There is a fantastic lineup of speakers and looks to be one of the highlights of the MedChem calendar. Early career scientists can also take part in a Medicinal chemistry workshop on the Sunday afternoon, a great way for people to learn medicinal chemistry and meet other scientists in a fun and informal setting.

You can register here both RSC and SCI members get a reduced rate, and despite the slightly confusing page on the SCI website you don't have to be a member to attend, just select "Event Member FREE from the dropdown menu and you can register for the event without membership.

Screenshot 2019-06-05 at 20.25.03

Twenty Years of the Rule of Five

It has been over twenty years since Lipinski published his work determining the properties of drug molecules associated with good solubility and permeability. Since then, there have been a number of additions and expansions to these “rules”. There has also been keen interest in the application of these guidelines in the drug discovery process and how these apply to new emerging chemical structures such as macrocycles.

This meeting aims to have a look at the impact the Ro5 has had on drug discovery and as well as looking to the future and how we use these rules in the changing drug compound landscape as drug discovery moves into novel areas of chemistry.

Ro5-webimage-2

There is a very exciting group of speakers and the timetable has been designed to allow a panel discussion after each session. Given the topic and the speakers I'm sure these will be entertaining sessions.

You can register here and there are discounts for RSC members

Twitter hashtag - #RuleofFive2019

European Lead Factory looking for novel screening programmes again

The European Lead Factory has been funded for another round of screening activities but under a new name European Screening Centre: unique library for attractive biology ESCulab. Over the next five years, the European Lead Factory will initiate 185 new drug discovery projects by screening medically relevant drug targets from European researchers, small and medium-sized enterprises and pharmaceutical industry against the ELF library of 550,000 unique chemical compounds.

The European Lead Factory was launched in 2013 and set up a joint collection of half a million compounds and a state-of-the-art high throughput screening centre. By the time the project ended last year, they had delivered results to researchers in universities, small biotechs and large companies across Europe, helping them to identify potential new drug candidates and breathing new life into a range of disease areas. In many cases, the seeds sown by the European Lead Factory resulted in new patents, partnering deals, and two start-ups. Now, a new IMI project, ESCulab will build on the work of the European Lead Factory. This means that researchers with drug targets can apply to screen the project’s compound collection for hits and get help developing any compounds further if they like. Jon de Vlieger, coordinator of the ESCulab consortium at Lygature, said: ‘It’s truly exciting to continue the onboarding of new and innovative proposals for screening and provide high quality starting points for drug discovery to academics and SMEs throughout Europe. In an effort to broaden our scope we are not only looking for target-based approaches, but now also enable phenotypic screens.’

You can apply here. If you don't have an assay in a format suitable for ultra high-throughput screening it is worth noting that the Wellcome Trust have small awards designed to help with the technology change required for HTS.