Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
July 26, 2026Science

Late-stage functionalization with strain-release warheads enables tunable covalent inhibition

View Full Paper
Ask AI
Bookmark
Share

Authors

ZSZachary P. ShultzMoffitt Cancer CenterALAnsar Lee-SamMoffitt Cancer CenterYCYun‐Pu ChangMoffitt Cancer Center

Discussion

Loading...

Member takes

Implication

Randomized trial evaluates strain-release warheads for selective protein targeting in mice, suggesting a novel approach for drug design.

Key Points

  • The aim is to develop a selective covalent inhibition strategy using modular strain-release warheads.
  • Developed a sulfur(IV) reagent platform for late-stage installation of functional motifs.
  • Demonstrated cysteine-selective engagement with modular covalent reactive groups.
  • Conducted preclinical studies in mice to validate efficacy and safety.
  • Achieved complete cysteine selectivity with strain-release CRGs.
  • Showed effective bioisosteric replacement of acrylamides in FDA-approved compounds.
  • Validated promising outcomes for next-generation covalent drug design in preclinical settings.

Cite This Study

Shultz et al. (2026) studied this question.

synapsesocial.com/papers/6a65a6b5d3aea3239cd77d92https://doi.org/10.1126/science.adx7219
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Regioselective hydroamination of unactivated olefins with diazirines as a diversifiable nitrogen source2024 · 17 citations
  2. 2Features and development of Coot2010 · 30,454 citations
  3. 3The Protein Kinase Complement of the Human Genome2002 · 8,282 citations
  4. 4phenix.model_vs_data: a high-level tool for the calculation of crystallographic model and data statistics2010 · 131 citations
  5. 5A Medicinal Chemistry Perspective on FDA-Approved Small Molecule Drugs with a Covalent Mechanism of Action2025 · 32 citations