Sebastian Greenhough

Fast and Reliable NMR-Based Fragment Scoring for Drug Discovery Fragment-Based Drug Discovery (FBDD) is a powerful strategy used in the development of new therapeutics. Molecular fragments are screened against a target protein, where interactions are typically characterized by a low affinity. Nuclear Magnetic Resonance (NMR) spectroscopy is well-suited to detect weak protein–ligand interactions and is therefore often used in FBDD. However, while NMR is very effective in initial screening, follow-up NMR experiments to measure binding affinities (i.e., KD values) are labor-intensive and time-consuming. To address this challenge, we have developed an innovative SHARPER NMR fragment scoring technique. The high sensitivity of SHARPER NMR dramatically reduces the data acquisition times, allowing faster and more accurate quantification of fragment KD values from ligand titration curves. To further accelerate fragment scoring, a machine learning model was developed that accurately ranks fragment affinities from only two SHARPER titration points. The resulting integrated method, termed “ML-boosted 1H LB SHARPER NMR”, produced significant time savings; using a 600 MHz QCI cryoprobe, KD values of up to 144 ligands in a day could be determined under our conditions, compared with only a handful achievable by traditional approaches. The proposed methodology will shorten the transition from hits to lead compounds, accelerating the drug discovery process by rapidly and reliably evaluating fragment binding, providing informed decision-making in the early stages of FBDD.

Nice paper just out from our NMR guys describing an accelerated method for measuring and scoring fragment binding affinities. pubs.acs.org/doi/10.1021/...

Biosciences Student Placement (Lab based) Cancer Research Horizons Biosciences Student Placement (Lab based) £23,000 plus benefits Directorate: Research & Innovation Contract: Fixed Term Contract 52 weeks Hours: Full time 35 hours per wee...

Undergraduates, we are recruiting! Come and join us at the @cruk-si.bsky.social in Glasgow for your industrial placement year. Start date September 2026. Great lab, great people, great city. Take a look!

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Kick off against cancer I’m raising money for Stand Up To Cancer to help fund life-saving research. Donate to participate in or simply cheer on the players in a charity football match played at the Garscube sports complex on...

Join us TODAY up on the Garscube artificial pitch at 1.15pm for Beatson Galaxy vs Wolfson Wolves, all in aid of Stand Up to Cancer.

60 minutes, 9v9, star-studded line-up. See you there!

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Kick off against cancer I’m raising money for Stand Up To Cancer to help fund life-saving research. Donate to participate in or simply cheer on the players in a charity football match played at the Garscube sports complex on...

A colleague is organising a charity football match next week to raise money for @su2c.bsky.social. It will feature some high-impact hotshots from @cruk-si.bsky.social and @uofgcancersciences.bsky.social so please take a look and come along if you can! fundraise.cancerresearchuk.org/page/kick-of...

Update: Mini quiches not bad and some interesting science too. It’s a shame the IP landscape around organoids is so restrictive as I’d like to see more use of them in drug discovery.

Organoids Are Us 2025 is happening at the Scotland Institute this week. I didn’t sign up but might sneak a look at the posters and/or buffet later.

Things like this don’t surprise me, but I wish we could stop talking about biology in terms of rules. All we really have are models, which either have real-world applications or they don’t. Keep breaking those rules, ants.

Saw the number plate P53 APC today and can only assume that I work with whoever owns it.

Read all about our small molecule pan-Ras inhibitors below! A 15-year effort from a team who still can’t get enough of near-impossible drug targets. I was only at the fringes of the project myself but pleased to have helped out here and there. Great work all!

René Bernards addressing the conference auditorium in the closing keynote.

Finishing out in style with a thought-provoking address from René Bernards on therapeutic overactivation of oncogenic signalling.

A great final day with a strong showing for immunogenic cell death including the first clinical data I’ve seen combining IAP & PD-1 inhibitors. Exciting! #BACR2025

All done with day 2 of #BACR2025. Lots of great immune stuff today - I believe neutrophils were mentioned more than 500 times but I’m here for it.

The Scott Monument in Edinburgh on a sunny morning.

Back in Edinburgh for day 2 of the BACR meeting. A bit nostalgic for my old commute, but I’m glad I don’t now have to get a bus to Little France. Or Roslin.

A busy conference auditorium awaits the first speaker.

The ornate ceiling of the Great Hall featuring gold pillars, statues, elaborate plasterwork and a chandelier.

The Progress Pride flag flies outside the main entrance.

Day 1 of the British Association for Cancer Research 65th Anniversary Meeting. Some good stuff on DNA repair, nonsense-mediated decay, epigenetics, dormancy, metabolism and lots more.

Nice venue too - The Royal College of Physicians of Edinburgh. Back again tomorrow! @thebacr.bsky.social #BACR2025

Congratulations on the move! I did my undergrad in Bath and it’s one of my favourite cities in the world.

The Francis Crick Institute on a sunny spring day.

Regent’s Canal on a sunny day. Barges, trees and waterfowl are visible.

Ducks on Regent’s Canal, with greenery and a heron on the bank.

Enjoyed visiting the Crick for the first time this week. Also if you’re in the area and need a breather then the nearby stretch of Regent’s Canal is lovely.

Scientist Strategic team efforts. Seamless synergy. Tangible results.  Scientist – Bioscience team, under the leadership of Stuart Farrow £33,700 - £38,150 (dependent on experience) plus benefits (includes up t...

We are currently recruiting for a scientist with a background in cell biology or immunology. This is a permanent, lab-based position at our site in London. Take a look! cancerresearchuk.wd3.myworkdayjobs.com/en-US/Extern...

If you’re looking for an exciting immuno-oncology postdoc position in a great city then I would advise applying for this!

An Athena Swan Gold Award printed cake, ornately presented on a table with various other gold-themed cakes, bottles of sparkling wine, gold balloons & napkins, a cake knife and a server.

The Athena Swan Gold Award celebration was genuinely better than quite a few weddings I’ve been to.

I’m very glad to have been able to help out with this as a member of the @scs-voice.bsky.social committee over the past few years. Great work everyone!

I’m a little late to the party, but this is a great read.

Just registered for this. Should be good!

Principal Scientist (Biochemistry/Enzymology) 4,000 professionals, 0 days wasted, 1 incredible purpose. Together, we are beating cancer. Principal Scientist – Biochemistry/Enzymology Starting salary: From £50,400-£57,400 per annum depending on ex...

We’re currently recruiting for a biochemist, to be based here in Glasgow at the @cruk-si.bsky.social or otherwise down in Cambridge. Take a look, and obviously choose Glasgow! cancerresearchuk.wd3.myworkdayjobs.com/en-US/Extern...

Hi everyone, it’s been a while!