Inlay

Could be useful if one has a robust SAR dataset... Structural optimization of drug molecules with incrementally trained language models ino.to/90PNYsh

Good one today from @dereklowe.bsky.social mRNA Vaccines: What's the Adjuvant? | Science | AAAS www.science.org/content/blog...

Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design

Identification of an STING inhibitor targeting the allosteric transmembrane domains: Cell Chemical Biology www.cell.com/cell-chemica...

[ASAP] Evaluation of Oral PROTAC Guidelines: Efflux Ratio Outweighs Chameleonicity Descriptors ino.to/ed4aPtD

Massive barcode-free chemical screenings enable the discovery of bioactive macrocycles with passive membrane permeability ino.to/IwMIfRQ

Roche takes 'leap of faith' with $20M bet on C4T’s antibody-targeted protein degraders ino.to/6xOeu9R

Good summary of the induced proximity phosphorylation space; still waiting for this to be reduced to practice for therapeutic value in the clinic..... www.cell.com/cell-chemica...

Machine learning–driven optimization of drug candidates remains a central challenge in medicinal chemistry, particularly when attempting to improve potency without relying on external scoring function...

Proteins lacking defined ligandable pockets remain challenging drug targets. Here, we develop a molecular glue-based PROTAC (MGPROTACs) approach that chemically conjugates a molecular glue stabilizer ...

Chen et al. introduce Y-320, a potent allosteric STING inhibitor that uniquely binds to the transmembrane domain instead of the canonical binding pocket, thereby blocking STING activation and traffick...

Revolution Medicines reported that its experimental KRAS inhibitor, called daraxonrasib, succeeded in a registrational trial for pancreatic cancer.

Oral bioavailability of PROTACs, which often fall outside the Rule-of-Five space, is still not perfectly understood. Thus, the design of orally bioavailable PROTACs remains challenging. Chameleonicity...

Synthetic macrocycles are promising therapeutics; however, most high-throughput discovery platforms rely on genetically encoded libraries of large peptide macrocycles, which are typically not optimized for drug-like properties. Here, the authors report CycloSEL (Cyclic Self-Encoded Libraries), an end-to-end workflow that screens synthetic macrocycle libraries enriched in drug-like ‘beyond rule of five’ features, based on affinity selections and hit identification by tandem mass spectrometry.

Roche has joined its Big Pharma peers in the emerging degrader-antibody conjugate (DAC) space, paying C4 Therapeutics $20 million upfront and committing more than $1 billion in milestones | Roche has joined Big Pharma peers in the emerging degrader-antibody conjugate space, paying C4 Therapeutics $20 million upfront and committing more than $1 billion in milestones to partner on two oncology targets.

Targeted protein degradation is one of the fastest developing fields in medicinal chemistry and chemical biology. Despite significant development in assay technologies and inhibitor discovery, the dev...

Ke et al. review emerging proximity-inducing modalities—phosphorylation-targeting chimera, including PhosTACs, DEPTACs, PhoRCs, and PHICS—that modulate protein phosphorylation via an “event-driven” me...