David Puleo, Marina Nelen, Chinatsu Sakata, and Ryan Potts discussed "Degraders in the Era of Precision Oncology" in an #AACRdrugdev26 plenary session chaired by Danette Daniels. @danetteldaniels.bsky.social @pottslab.bsky.social

Excited about programming biology via induced proximity? Then mark June 2026 in your calendar and consider participating in the GRC Conference on Induced Proximity Modalities and Therapeutics that I am co-organizing with @danetteldaniels.bsky.social tinyurl.com/brtuffam

Congratulations to the two winners of the Women in TPD & Induced Proximity conference travel scholarships @jessicagraham1.bsky.social and Leyna Duong. We look forward to welcoming you at our #FCQC2025 in March! @womenintpd.bsky.social @danetteldaniels.bsky.social

Women in TPD & Induced Proximity@womenintpd.bsky.social · 2y ago

Congratulations to Jessica Graham from @crick.ac.uk and Leyna Duong from Stanford who have been awarded Women in TPD & Induced Proximity conference travel scholarships to attend the 4th Frankfurt Conference on Quality Control in Life Processes!

Thank you so much to the @womenintpd.bsky.social for this opportunity! What a fab initiative empowering women in science. Excited to connect in Frankfurt

Women in TPD & Induced Proximity@womenintpd.bsky.social · 2y ago

Congratulations to Jessica Graham from @crick.ac.uk and Leyna Duong from Stanford who have been awarded Women in TPD & Induced Proximity conference travel scholarships to attend the 4th Frankfurt Conference on Quality Control in Life Processes!

Kudos Jessica and Leyna! Looking forward to meeting both of you in Frankfurt ☺️

Women in TPD & Induced Proximity@womenintpd.bsky.social · 2y ago

Congratulations to Jessica Graham from @crick.ac.uk and Leyna Duong from Stanford who have been awarded Women in TPD & Induced Proximity conference travel scholarships to attend the 4th Frankfurt Conference on Quality Control in Life Processes!

Congratulations to both of you! @WomeninTPD first official scholarship award winners ☺️

Women in TPD & Induced Proximity@womenintpd.bsky.social · 2y ago

Congratulations to @alesalerno.bsky.social from University of Dundee CeTPD and Christine Ng from @stanford-chemh.bsky.social who have been selected as recipients of our conference travel scholarships to attend the Proximity-based Therapeutics Keystone conference @keystonesymposia.bsky.social!

If you are working on degradation of membrane proteins this work co-led by Camilla Ruffilli along with colleagues at AstraZeneca is a nice systematic look at best methods to quantitate and validate loss! www.nature.com/articles/s41...

Orthogonal validation of PROTAC mediated degradation of the integral membrane proteins EGFR and c-MET - Scientific Reports

Scientific Reports - Orthogonal validation of PROTAC mediated degradation of the integral membrane proteins EGFR and c-MET

nature.com

So happy to see the growth of our initiative to now offer conference scholarships! Apply below for consideration. Happy 2025 ☺️☀️☺️

Women in TPD & Induced Proximity@womenintpd.bsky.social · 2y ago

HAPPY HOLIDAYS and EXCITING NEWS!!! We are offering two conference scholarships for 2025 to early career scientists! One for the Keystone Proximity-Based Therapeutics Conference and one to Frankfurt Conference on Quality Control in Life Processes. Application and details: forms.gle/aP4n7HTujetb...

A look at why some targeted oncology drugs have succeeded in some areas and totally failed in others. The short answer: kill cancer cells - don't just slow 'em down.

Targeted Cancer Drugs, Succeeding and Failing

science.org

Congratulations Alejandra Rodríguez Gimeno on this review covering approaches to develop new E3 ligase binders/handles! chemistry-europe.onlinelibrary.wiley.com/doi/full/10....

Drug Discovery Approaches to Target E3 Ligases

Comprehensive review presenting the different drug discovery approaches that until now have been employed in academic and pharmaceutical settings to identify new E3 ligase small molecules ligands and...

chemistry-europe.onlinelibrary.wiley.com

New work out co-led by Xin Yu and colleagues at Baylor showing development of a selective RIPK1 degrader (VHL) and its synergy with anti-PD1 immunotherapy. Interesting potential combination to address resistance to and enhance activity of immune checkpoint inhibitors. www.nature.com/articles/s41...

Development of a RIPK1 degrader to enhance antitumor immunity - Nature Communications

It has been shown that targeting receptor-interacting protein kinase 1 (RIPK1) can improve response to immune checkpoint inhibitors. Here, using PROTAC technology, the authors report the design and ch...

nature.com

Work out co-led by Inés García Pérez and @crismayorruiz.bsky.social showing the importance of targeting KRasG12V for treatment of lung adenocarcinoma. Degradation of KRasG12V is achieved using dTAG knock-in, allowing them to building relevant mouse models. www.biorxiv.org/content/10.1...

Targeted KRAS(G12V) degradation elicits efficient and durable lung adenocarcinoma regression in vivo

Recent drug discovery breakthroughs led to the approval of KRASG12C inhibitors in lung adenocarcinoma (LUAD). Unfortunately, clinical responses remain limited due to rapid resistance onset. Proteolysi...

biorxiv.org

Thrilled to share a wonderful collaboration with Scott Armstrong, Florian Perner & Shellaina Gordon - exciting times ahead! www.biorxiv.org/content/10.1...

Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia

Understanding the molecular pathogenesis of MLL fusion oncoprotein (MLL-FP) leukaemia has spawned epigenetic therapies that have improved clinical outcomes in this often-incurable disease. Using genet...

biorxiv.org

Amazing new work from the lab of @aliceyting.bsky.social @stanfordmedicine.bsky.social @stanfordbiosci.bsky.social, engineered GPCRs for ligand-activated cell responses www.nature.com/articles/s41...

Synthetic GPCRs for programmable sensing and control of cell behaviour - Nature

Modular synthetic G-protein-coupled receptors with nanobody-based ligand-recognition domains can be designed and used to programme transgene expression, real-time fluorescence or endogenous G-protein ...

nature.com

Incredible meeting #CSChemBio2024 in San Francisco including talks from @fleurmferguson.bsky.social, @danetteldaniels.bsky.social, Michelle Arkin, Ingrid Wertz, and @mishtudey.bsky.social!

That awkward moment when someone publishes a paper saying that they can’t find any evidence that your compounds bind to what your own series of papers say that they bind to. . .

Do They Even Bind?

science.org

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets Refreshing to see papers that go to great pains to set the record straight being published in a high profile setting

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets - Nature Communications

Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but e...

nature.com

Excited to report our discovery of an important component of the oxidative stress response: the E3 ligase TRIP12. It acts as a chain elongation factor that amplifies CUL3-KEAP1 activity to drive NRF2 degradation as cells recover from stress. www.biorxiv.org/content/10.1...

Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12

The oxidative stress response is centered on the transcription factor NRF2 and protects cells from reactive oxygen species (ROS). While ROS inhibit the E3 ligase CUL3-KEAP1 to stabilize NRF2 and elici...

biorxiv.org

There are no shortcuts in drug discovery. And it takes incredible efforts to make sense of what you can find in the scientific literature. This is an excellent piece of work to quality check what has been claimed as a new avenue in targeted protein degradation (TPD). www.nature.com/articles/s41...

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets - Nature Communications

Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but e...

nature.com

We've now filled one #Epigenetics, Chromatin and Gene regulation starter pack. Thanks for all the enthusiasm and support, if you'd like to be listed @raduzabet.bsky.social has been hard at work getting part II up and running: go.bsky.app/SqLa3aw

My first Bluesky 🦋 post! So exciting to receive today the Epigenetic Drug Discovery book which includes our chapter on targeting chromatin remodeling complexes! #chemsky #chembio #tpd #foghorntx #oncology

📯📯NEW Chemical Biology Feed bsky.app/profile/did:... 📯List: >200 chemical biologists (probes, OC, PC, imaging): bsky.app/profile/did:... 📯Women in ChemBio Pack: bsky.app/starter-pack... 📯General #ChemBio Pack: bsky.app/starter-pack... 📯 #Photopharma: bsky.app/profile/trac... #chemsky 🧪 🔬

Building better predictive models for bioavailability of PROTACs using an iterative design-make-test-analyze approach of ~700 degraders. Work led by Zulma Santisteban Valencia and colleauges at AstraZeneca. pubs.acs.org/doi/10.1021/...

Closing the Design–Make–Test–Analyze Loop: Interplay between Experiments and Predictions Drives PROTACs Bioavailability

The drug development landscape is expanding to include drug modalities such as PROteolysis-TArgeting Chimeras (PROTACs) and peptides, offering possibilities for previously intractable biological targets. However, with their size and chemical nature, they diverge from established frameworks for the prediction of oral bioavailability. This evolution to larger and more complex molecules necessitates new methodologies and prediction models to continuously expand on bioavailability guidelines. We describe the high-capacity adoption of two chromatographic physicochemical assays and their application for iterative compound optimization to achieve oral bioavailability. We further describe how these data underpin the continuous refinement of internal machine learning models, which guide compound synthesis decisions in the molecular design phase. Based on data for a set of 691 PROTACs, and two project examples, we confirm a sweet spot for oral bioavailability at log D values higher than the norm for small molecules and show how experimental data and prediction models synergize to effectively drive chemistry optimization.

pubs.acs.org

An interesting story led by Alissa Guarnaccia, Jennie Lill, and Genentech colleagues of a small molecule induced co-factor binding swap, from disrupting TEAD:YAP complexes to promoting TEAD:VGLL4 repressive ones. A double whammy on YAP activity! Looks like a new glue? www.biorxiv.org/content/10.1...

TEAD-targeting small molecules induce a cofactor switch to regulate the Hippo pathway

TEAD proteins are the main transcriptional effectors of the Hippo signaling pathway and a pharmacological target in oncology. Most TEAD-targeting small molecules act by disrupting interaction with the...

biorxiv.org

DCAF1-based degraders of WDR5 and determination of this new class of ternary complex structures! Congratulations to teams at University of Toronto, SGC, and Ontario Institute of Cancer Research co-led by Rima Al-awar. www.nature.com/articles/s41...

Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity - Nature Communications

The authors show that DCAF1, a substrate receptor of CUL4 and EDVP E3 ligases, can be recruited by PROTACs to degrade the cancer drug target, WDR5. They also report the crystal structures of PROTAC te...

nature.com

go.bsky.app/3VPQofn Have a look at the Ubiquitin and Ubls list Lisa :-)

The starter pack the TPD community has been waiting for: go.bsky.app/CE2P2Yh

Chemoproteomics starter pack, thanks mostly to @stephanhacker2.bsky.social's strong network go.bsky.app/JKJ1ZHt