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Happy to share our @chemicalscience.rsc.org paper where we extract a SAR model from HT crystallographic readouts of fragment elaborations in crude reaction mixtures!
Thanks to @kate-fieseler.bsky.social for co-writing and @philbiggin.bsky.social!
doi.org/10.1039/D5SC...
#MyFirstChemSci #FBDD #D2B

Have you tried changing from a number scale to a smiley face scale? Our #d2b (direct to baby) experts have found that early age engagement responds better to a smiley face

Chris Miller and Andrew Ratcliffe are at Booth 513 at #DOT2025, drop by to find out more about how we can drive your lead discovery project forward.

We'd also be delighted to discuss our #D2B services, highlighted during our talk. Looking forward to a day of good discussions.

#Domainex will be attending Discovery on Target in Boston from the 22nd September. Come find Chris Miller and Andrew Ratcliffe at Booth 513 if you are attending.
Don't miss AJ's talk on 'Direct-to-Biology Enabled Drug Discovery' to find out more about our #D2B platform.

Direct Cellular Screening of Pd-Mediated Arylation of Cyclic Peptide Binders Targeting Ubiquitin Chains: Toward Modulating NEMO Liquid–Liquid Phase Separation Ubiquitination is a critical post-translational modification that regulates key cellular processes such as protein degradation and DNA damage repair. Targeting a specific type of ubiquitin chain (e.g., Lys48 or Lys63-linked ubiquitin chain) via cyclic peptides presents a new strategy to modulate biological processes with therapeutic potential for various diseases. However, such a strategy remains challenging due to the obstacles of cell permeability and bioactivity. Here, we present a new method that directly assesses these parameters by integrating palladium-mediated Cys arylation with direct cellular screening. Using CP4, a previously identified cyclic peptide modulator of Lys63-linked ubiquitin chains, we generated a focused library of arylated analogues and optimized the Pd-mediated arylation for direct cellular screening. We discovered a new analog, CP-P12-ArH, that demonstrated enhanced binding affinity and robust bioactivity, as evidenced by increased γ-H2AX phosphorylation and apoptosis induction in cancer cells. Furthermore, CP-P12-ArH effectively inhibited the in vitro formation of NF-κB essential modulator (NEMO) biomolecular condensates by disrupting the elongation of Lys63-linked ubiquitin chains, offering a novel way to modulate NF-κB signaling. This work establishes a generalizable platform for the rapid optimization of cyclic peptide therapeutics targeting protein–protein interactions.

Interesting paper by the group of Ashraf Brik in @jacs.acspublications.org. Pd-mediated modification of cyclic peptides allows to combinatorially generate S-arylated derivatives and directly screen them for activity in cells.

pubs.acs.org/doi/10....
#ChemSky #ChemBio #DirectToBiology #D2B

At #Domainex, we are always looking for ways to improve and update our services. We have expanded the scope of our #D2B platform by testing the compatibility of a range of #assay formats and reaction types. Find out more:
www.domainex.co.uk/services/dir...

Image shows a schematic of areas of SAR expansion and structure and assay data for (R)-11. Images are taken from Bush et al. with permission from the authors.

In our latest blog, we highlight work from GSK, in which they use a #D2B approach to drive optimisation of a cell-active covalent inhibitor of WRN helicase.
www.domainex.co.uk/news/medicin...

Image shows two MINI 96 liquid handlers.

We’re pleased to share that we’ve just taken delivery of two MINI 96 liquid handlers from INTEGRA Biosciences! This exciting addition to our liquid handling capability will enable us to move even faster with our Direct-to-Biology projects.
#D2B #Direct2Biology #DrugDiscovery

Image shows a scheme of a D2B platform using orthogonally reactive linkers on the left. On the right, the chemical structures of two compounds of interest are shown; KH1 and KH2.

In our latest blog, we highlight a paper describing the discovery of a #CNS active GSK3 degrader using “orthogonally reactive linkers” and a direct-to-biology approach.
www.domainex.co.uk/news/medicin...
Find out more about #D2B by getting in touch with us via enquiries@domainex.co.uk

Domainex at the 9th RSC-BMCS Symposium on Mastering Medicinal Chemistry with their poster.

#Domainex is at the 9th RSC-BMCS Symposium on Mastering Medicinal Chemistry today. If you are there, take a look at our poster "Using Direct-to-Biology in a Spectral Shift-PoLiPa Platform to Enable Fast Fragment Follow-Up for Adenosine A2a Antagonists"
#D2B #SpectralShift #FBDD #DrugDiscovery

Oh no. #D2B http://t.co/WujDWESe

I can see my breath, which is a good thing because it means I'm still breathing. #D2B

This is pretty much how #D2B attendees communicated RT @JeffSvoboda @steakNstiffarms nice to you tonight' Eike robi tonight id... it'$ :8+3?

9+ Sanrio Clothing Themes For Adults (Kawaii Outfit Aesth... Hello Kitty, My Melody, and Keroppi might seem like a str...

It's @steakNstiffarms & @sarbucks, after dark. #D2B http://lockerz.com/s/151209873

With the arrival of @MsWa10za #D2B suddenly is too sophisticated. #nomojo #smartwomen #kryptonite

"I'm so sick of people and their Marcy Playground." #jihad4DJ #D2B

@ESPN_BigTen @elevenwarriors #D2B Tell 'em Craig James says "hi." #5dh

It has been determined: @lukezim is the #AngelOfQueefcore. Everywhere he goes, Matchbox 20 "mysteriously" comes on. (cc: @edsbs) #D2B

ImageShack - Best place for all of your image hosting and... Unlimited space to host images, easy to use image uploade...

Carving punkins with the kids instead of #D2B. Stupid fatherhood. See you @ #E2B. http://yfrog.com/hsexqmaj

#D2B #jihad4DJ @djbrnz RT @elevenwarriors: PSA: Drink Too, Brutus is on the first floor of Bar Louie. Southeast corner of the venue.

9+ Sanrio Clothing Themes For Adults (Kawaii Outfit Aesth... Hello Kitty, My Melody, and Keroppi might seem like a str...

Look, it's @sarbucks' dinner. #D2B http://lockerz.com/s/151119799