Open Source Antibiotics is a consortium of researchers interested in open ways to discover and develop new, inexpensive medicines for bacterial infections.
All the structures of the molecules on the project are openly available in a spreadsheet https://docs.google.com/spreadsheets/d/168-a1_l51Nfbms67eG8zU8p-EhEtEO26FUzRInbu7fY/edit#gid=2078630269 feel free to have a browse.
Often when moving into a new therapeutic area it takes a while to pick up all the terms and acronyms, and antimicrobial research has some of it's own, not sure what a MIC is then head over to the REVIVE Antimicrobial Encyclopaedia and search.
The REVIVE Antimicrobial Encyclopaedia includes definitions of terms from the field of antimicrobials including ‘Active Pharmaceutical Ingredient’, ‘Bacterial efflux’ and ‘Minimum Inhibitory Concentration’. Each term has links for users to find more information on the subject and wherever available there are also links to REVIVE content such as webinar recordings and Antimicrobial Viewpoints on the subject. Some terms also include bespoke explanatory videos with clear diagrams featuring REVIVE experts.
REVIVE is a space for everybody with an interest in antimicrobial R&D. The Global Antibiotic Research and Development Partnership (GARDP) is a not-for-profit organization developing new treatments for drug-resistant infections that pose the greatest threat to health. We were created to ensure that everyone who needs antibiotics receives effective and affordable treatment, no matter where they live. We aim to develop five new treatments by 2025 to fight drug-resistant infections, focusing on sexually transmitted infections, sepsis in newborns and infections in hospitalized adults and children.
My RSC membership renewal form has just dropped though the letterbox.
It is the ideal time to think about joining one of the RSC Interest groups.
Interest groups are scientific networks run by members for their community. Each group is themed around a specific area or application of the chemical sciences. They organise an annual series of events to cater for both their members and the wider scientific community. These events vary from: multi-day conferences and workshops to training events.
If you are interested in the computational side of drug discovery why not join the Chemical Information and Computer Applications Group CICAG code 86.
The closure date for the latest round of proposals for screening at the European Lead Factory is January 2021
The European Lead Factory welcomes drug targets in all therapeutic areas. Interested? Submit your screening proposal now. The next deadline to apply will be in January 2021.
Following the UK’s exit from the European Union on 31 January, we are pleased to confirm that the European Lead Factory still welcomes screening proposals from UK researchers.
You can read more about the screening facility here https://www.europeanleadfactory.eu/node/353.
The details of how to submit are here https://www.europeanleadfactory.eu/how-submit/drug-target-assays/how-it-works.
I've written about the ELF here.
I just thought I'd share this email
Dear Friend of Open Source Antibiotics (OSA),
It's been a busy few months in OSA. Recent activity is being captured in weekly public Zoom meetings (every Friday at 2pm London at https://ucl.zoom.us/j/92800004715), and you can see the details in the recordings of those meetings (like this one) and the associated "Github Issues" (like this one).
But as part of those discussions we were wondering about the best way to update everyone quickly. While OSA uses Twitter, there is no good substitute for a short email. So this is the first, short OSA news email. Three points:
- We have guessed you're interested in receiving occasional emails about OSA. If you're not, just email us back to say you'd like to opt out. Nobody likes spam.
- Please forward this to anyone you think might be interested in antibiotics or drug discovery or open science. As an open project, everything is in the public domain, and everyone is welcome.
- To keep things short, each news email has a limit of three items. If you're interested in learning more, then each project has a wiki (current project status, like this) and the Issue Tracker (current To Do list and discussion, like this).
- We have confirmed the activity vs MRSA of the diarylimidazoles (exemplar compound OSA821 shown below), originally discovered and explored by Alvaro Lorente and Bill Zuercher at UNC Chapel Hill. A new potency screen is being performed this week at UCL by Paul Stapleton, and includes about 30 compounds that have been donated to the project via Ben Perry (DNDi). This time our potency assay will include a parallel screen of select compounds vs VRE, to see if there is activity vs other high priority Gram +ves.
- A key aim of the project is to solve the rapid clearance of the known actives. New data from Sue Charman's lab gave clues as to which compounds to investigate next, and we are finalising negotiations for some pro bono work from a UK company towards identification of possible metabolites.
- The mechanism of action of these compounds is unknown, but Lee Graves's lab at UNC are in the middle of some MIBs experiments that we hope will reveal, by the end of October, some key new insights into how the compounds work.
You can read more about the Open Source Antibiotics on GitHub https://github.com/opensourceantibiotics.
Why not swing by and have a browse.
The latest release of the Open Targets Platform - 20.09 - is now available at https://www.targetvalidation.org/.
This release sees the addition of ClinGen to the expert curated evidence sources for rare disease genetics that includes UniProt, the Genomics England PanelApp, and Gene2Phenotype.
This latest update includes 27,610 Targets, 13,944 Diseases, 8,419,186 Evidence and 6,551,303 Associations
Artificial Intelligence and Augmented Intelligence for Automated Investigations for Scientific Discovery (AI3SD) are running an Online Guest Lecture Series this summer. The full seminar list is here.
If you missed a presentation or want to replay it, all the presentations are on the AI3SD YouTube channel.
The RSC Biological and Medicinal Chemistry initiated a Hall of Fame a short while ago and I'd like to highlight the relevant page of the BMCS website.
The Hall of Fame is to recognise prominent chemists for outstanding, sustained, contributions to any area of interest to the BMCS, eg medicinal chemistry, agriscience, biooorganic chemistry, chemical biology. This is an Individual award to recognise prominence and significant, sustained, scientific impact in the field of medicinal chemistry, agriscience or chemical biology, including teaching excellence, outstanding contributions to the BMCS, or any combination thereof.
The first inductee to the BMCS Hall of Fame was Professor C Robin Ganellin FRS, Emeritus Professor of Medicinal Chemistry at University College London. He co-discovered histamine H2-receptors with James Black and co-invented the anti-ulcer drug cimetidine. He co-discovered butabindide, an inhibitor of the enzyme tripeptidyl peptidase II, and co-invented the histamine H3-receptor antagonist drug, pitolisant.
Cimetidine was the first histamine H2 receptor antagonist drug that inhibits stomach acid production and used in the treatment of heartburn and peptic ulcers.
Oral bioavailability is 65% and it has a half-life of 2 hours.
Butabindide is an inhibitor of the enzyme tripeptidyl peptidase II designed as an anti-obesity drug.
The histamine H3-receptor antagonist Pitolisant, is used for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy
Pitolisant is well absorbed (90%) and has an elimination half-life of 10-12 hours.
The 2019 inductee was Sir Simon Campbell CBE FRS FMedSci who is probably best known for his work leading to Doxazosin, for high blood pressure and angina and Amlodipine – used to treat high blood pressure and prostrate enlargement.
Doxazosin is a α1-selective adrenergic blocker in the quinazoline class of compounds
Oral bioavailability is 65% and elimination half-life 22 hours, , it highly plasma protein bound (98%). Hepatic metabolism of doxazosin produces inactive O-demethylated and C-hydroxylated metabolites.
Amlodipine is a long acting calcium channel antagonist, it blocks L-type calcium channels in muscle cells and N-type calcium channels in the central nervous system.
Amlodipine is well absorbed by the oral route with a mean oral bioavailability around 60%; the half-life of amlodipine is about 30 h to 50 h, it highly plasma protein bound (97.5%). Renal elimination is the major route of excretion with about 60% of an administered dose recovered in urine, largely as inactive pyridine metabolites. Amlodipine is on the World Health Organisation's List of Essential Medicines.
The COVID Moonshot is an ambitious crowdsourced initiative to accelerate the development of a COVID antiviral. We work in the open with no intellectual property constraints. This way, any scientist can view submitted drug designs and experimental data to inspire new design ideas. We use our cutting-edge machine learning tools and Folding@home's crowdsourced supercomputer to determine which drug designs to send to our partners to make and test in the lab. With each drug design tested, we get closer to our goal.
It is sometimes difficult to cross-reference compounds between multiple sources so I've downloaded the compounds with associated data calculated InChiKeys and then used the InChiKey to link compounds from different sources within Vortex. This means you have the biochemical data together with PDB code (if available) or the fragalysis code for the crystal structure. I've also annotated with identifiers from multiple databases (ChEMBL, PubChem etc.), calculated physicochemical properties (LogP/D, TPSA, HBD/A etc) and then exported in sdf format. I've also clustered the structures to aid navigation.
You can download the zipped sdf file here.
Updated. I was asked if I could provide this file in SMILES format so here it is.
I plan to try and have a look at ways to visualise the data when I can find some free time.
When helping to enhance screening collections I'm sometimes asked to exclude "prohibited precursor chemicals", these are chemicals that might be used in the manufacture of illegal drugs.
The effective control of chemicals used in the illicit manufacture of narcotic drugs and psychotropic substances is an important tool in combating drug trafficking. These chemicals, known as ‘precursors’, also have legitimate commercial uses as they are legally used in a wide variety of industrial processes and consumer products, such as medicines, flavourings and fragrances.
I'm aware of this list on the UK Government website https://assets.publishing.service.gov.uk/...PRECURSORCHARTDomesticJan2014.pdf, and the listing from INCB http://www.incb.org/documents/PRECURSORS/REDLIST/2020/RedList2020E.pdf, however I'm sure it far from complete.
Does anyone know of a more complete listing? Preferably in a chemically intelligent form