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Cambridge MedChem Consulting

21st RSC / SCI Medicinal Chemistry Symposium

Registration for the 21st RSC / SCI Medicinal Chemistry Symposium Monday-Wednesday, 13th-15th September 2021 hosted at Churchill College, Cambridge, UK is now open. Twitter hashtag - #CamMedChem21

As usual there is a stella lineup of presentations and there is still time for some submissions.

I'd like to highlight one talk that is close to my heart. Ed Griffen will talking about The COVID Moonshot: SARS-CoV2 oral antiviral therapeutics from an Open Science global collaboration.

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.

This talk will be in the late breaker session and because of the open nature of the project it will be a chance to really see the very latest results "hot off the press".

You can have a look at the latest results here now. https://covid.postera.ai/covid.

30th April: Late breaker and early poster deadline
23rd July: Final poster deadline

Registration link https://www.maggichurchouseevents.co.uk/bmcs/cmc21/index.htm

Do you include chiral fragments in your screen?

Fragment-based screening has become increasingly popular over the last 15 years and has proven to be a viable alternative to high-throughput screening.

A little while ago I posed the question "Do you include chiral fragments in your screen?" And the results were interesting. Whilst many, many folks clicked on the link very few actually responded to the poll, perhaps something people are thinking about but don't have an answer?

For those that did respond it seems that very few actively exclude chiral fragments.

chiralfragmentspoll

Of those that included chiral fragments the responses were pretty evenly split between those that include racemates and only worry about the enantiomers if they appear as a hit, those that only include racemates if the individual enantiomers are available and those that only include individual enantiomers.

One of the arguments against including chiral fragments has been it increases the complexity of the fragments and as the ligand/receptor match becomes more complex the probability of any given molecule matching falls. However, biological targets are almost invariably chiral and selectivity often relies on stereochemical features.

One of the key attractions of fragment screening is the ability to explore/validate hits without committing significant chemistry resources, so I’d argue that the ready availability of related analogues ought to be part of the library selection criterion and by extension having access to the individual enantiomers should be an important consideration.

Chemical Probes

A really interesting review of the Chemical Probes portal

2020 was the first year of visible activity on the Chemical Probes Portal since 2017, with 115 probes added and over 500 compounds now included on the Portal. To celebrate, we’re highlighting ten of the best probes added to the Portal and evaluated by our Scientific Advisory Board in 2020. These probes are selective, potent, cell-active molecules that are rated four stars for use in cells and target new proteins or have new mechanisms of action. They include probes for previously ‘undruggable’ cancer targets, compounds that target GPCRs, epigenetic modulators and PROTACs.

Full details are here https://www.chemicalprobes.org/news/2020s-top-probes.

kras

Open Targets Platform beta test

If you have a little time why not drop by the Open Targets website and give the beta test version and give them some feedback. Full details are in the blog post.

The beta version makes the most of the data from the recent 21.02 release and you can also interrogate the data using the brand new GraphQL API.

In particular, this version features:

  • Redesigned evidence pages
  • Updated drug profile pages
  • More complete disease profile pages

Open Targets is a public-private partnership that uses human genetics and genomics data for systematic drug target identification and prioritisation. The current focus is on oncology, immunology and neurodegeneration.

Generating and interpreting the data required to identify a good drug target demands a diverse set of skills, backgrounds, evidence types and technologies, which do not exist today in any single entity. Open Targets brings together expertise from seven complementary institutions to systematically identify and prioritise targets from which safe and effective medicines can be developed.

March webinar: High Content Screening at the European Lead Factory

The next European Lead Factory webinar will take place on Thursday 11 March from 11:00-12:00 (CET). In this webinar, we will focus on High Content Screening with a presentation by Professor Jason Swedlow, head of the National Phenotypic Screening Centre at the University of Dundee.

More details and registration here https://www.europeanleadfactory.eu/node/375

MAIP: a web service for predicting blood‐stage malaria inhibitors

An interesting publication Bosc, N., Felix, E., Arcila, R. et al. MAIP: a web service for predicting blood‐stage malaria inhibitors. J Cheminform 13, 13 (2021). https://doi.org/10.1186/s13321-021-00487-2.

We describe the development of an open-source software platform for creating such models, a comprehensive evaluation of methods to create a single consensus model and a web platform called MAIP available at https://www.ebi.ac.uk/chembl/maip/. MAIP is freely available for the wider community to make large-scale predictions of potential malaria inhibiting compounds. This project also highlights some of the practical challenges in reproducing published computational methods and the opportunities that open-source software can offer to the community.

The code to standardise the compounds and train the models is available on GitHub:

standardiser: https://github.com/flatkinson/standardiser.

ModifiedNB: https://github.com/chembl/ModifiedNB.

mmv_train_image: https://github.com/chembl/mmv_train_image.

The ready to use Docker image to generate the models is available at https://hub.docker.com/r/chemblgroup/mmv_train. The MAIP platform is available at https://www.ebi.ac.uk/chembl/maip/.

New GARDP webinars

gardp-logo

25 February: 'From discovery to IND: Roadmap to a successful antibacterial project' with Patricia Bradford and Alita Miller, moderated by Michael Mourez. Register here: https://attendee.gotowebinar.com/register/8974462807057685772?source=spark

4 March: 'Learning from COVID-19 to tackle the silent pandemic of antibiotic resistance' with Marc Mendelson, Joanne Liu and Manica Balasegaram. Register here: https://attendee.gotowebinar.com/register/3151890131955239691?source=spark

24 March: 'Discovering and developing new treatments for tuberculosis' with Nader Fotouhi, moderated by Lydia Nakiyingi. Register here: https://attendee.gotowebinar.com/register/394450209091477264?source=spark

As always, keep an eye on our website https://revive.gardp.org/webinars to find new webinar announcements and recordings of previous webinars.

ChEMBL 28 has been released.

I see that a new version of ChEMBL has been released. Chembl 28

  • 2,680,904 compound records
  • 2,086,898 compounds (of which 2,066,376 have mol files)
  • 17,276,334 activities
  • 1,358,549 assays
  • 14,347 targets
  • 80,480 documents

chembl28

Career choices when faced with changes of life

As someone who had to make a major career change due to personal circumstances I really recommend this sort of webinar that has been organised by the RSC.

Career choices when faced with changes of life

Join Career Consultants Cath Elmer and John Toscano who will spend an evening helping you give your working lives a well-deserved health check! Together we will look at some of the reasons career circumstances can change - out of choice or otherwise. We will discuss some of the career theories behind our decision-making processes to help us assess where we are and be better prepared for the future. This interactive event will be of interest whatever stage of your career.

Thursday 15th April 6:00-8:00 pm

Link https://www.rsc.org/events/detail/46366/career-choices-when-faced-with-changes-of-life.

Fluorine Fragment Library

Key Organics have expanded the BIONET Fluorine Fragment Library which now includes 719 fluorinated fragments. All 719 fragments in the Fluorine Fragment Library have been analysed by 19F NMR and 1H NMR for:

  • Structure verification
  • Purity
  • Measured solubility in PBS buffer ≥ 100μM
  • Aggregation.

The calculated physicochemical properties of the library are shown below. They have also been filtered using PAINS and Lilly MedChem rules.

BIONETFluorineFragmentLibrary

There are more Fragment Collections described here.