I've written a page in the Drug Discovery Resources on covalent inhibitors.
This publication suggests this area is going to become more important "An activity-guided map of electrophile-cysteine interactions in primary human immune cells" https://www.biorxiv.org/content/10.1101/808113v1.
Here, we present a global map of cysteines in primary human T cells that are susceptible to covalent modification by electrophilic small molecules. More than 3000 covalently liganded cysteines were found on functionally and structurally diverse proteins, including many that play fundamental roles in immunology.
Great news! European Lead Factory has restarted.
Pivot Park Screening Centre has successfully completed the first ultra-High Throughput Screening in IMI’s ESCulab project, and as such restarting the operations of the European Lead Factory. The screening on the European Compound Collection of ~500.000 compounds using a biochemical 1536-wells assay was finished within 4 days. Currently triaging of the UK owned program is ongoing within the Consortium, applying further biochemical and biophysical follow-up assays as well as the resynthesis of promising hits.
The programme is currently accepting proposals http://www.europeanleadfactory.eu/drug-target-assays.
A new initiative, great to see efforts in CNS diseases.
First call for proposals to the Psychiatry Consortium. Read more about the kind of projects the Psychiatry Consortium is looking to fund on the website https://md.catapult.org.uk/syndicates/psychiatry-consortium/?.
One of the advantages of being a consultant is that I can feel free to contribute to projects that I find interesting. So as well as working with a couple of Open-Source drug discovery projects (e.g. Open Source Antibiotics I can also follow a couple of rare disease programs.
This publication looks very useful History of rare diseases and their genetic causes - a data driven approach.
This dataset provides information about monogenic, rare diseases with a known genetic cause supplemented with manually extracted provenance of both the disease and the discovery of the underlying genetic cause of the disease.
More details of how the dataset was constructed.
We collected 4166 rare monogenic diseases according to their OMIM identifier, linked them to 3163 causative genes which are annotated with Ensembl identifiers and HGNC symbols. The PubMed identifier of the scientific publication, which for the first time describes the rare disease, and the publication which found the gene causing this disease were added using information from OMIM, Wikipedia, Google Scholar, Whonamedit, and PubMed. The data is available as a spreadsheet and as RDF in a semantic model modified from DisGeNET.
A very interesting read.
The latest Open Targets Platform 19.09 has been released. The latest release contains
27,024 targets 10,474 diseases 3.33 million pieces of evidence 7.78 million associations between targets and diseases
In addition, a number of Target Enabling Packages (TEP) provided by Structural Genomics Consortium have been included, there are more details here. Several new chemical probes have also been included.
I've updated the covalent inhibitors page to include details of two covalent fragment libraries that have been used in fragment screening.
A new initiative that should be very useful,
An event (with free registration) to foster the In silico Toxicology Community in the UK and beyond. Scientific contributions are as welcome as those on ongoing work, regulatory aspects, industry perspectives, databases, relevant software, journals etc. in the field. This event is meant to stimulate interactions and discussions, hence speakers are asked to present both about in silico toxicology approaches that are already useful to be applied at the current stage, as well as aspects that don't work that well right now, and where future developments are hence needed.
Venue 26 November 2019, Unilever Lecture Theatre, Department of Chemistry, University of Cambridge (CB2 1EW)
Full details and link for registration here In Silico Toxicology' Network Meeting 2019.
A small update to the Ester and Amide bioisosteres page.
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
- Calculating Physicochemical Properties
- Distribution and Plasma Protein Binding
- Molecular Interactions
- Kinase Inhibitors
- Acid Bioisosteres
- Aromatic Bioisosteres
- Solvation and desolvation
- Aspartic Acid Proteases
- CYP Interactions
- Fragment based screening
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%).
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.