EMBL Keynote Lecture: Chemical biology opens new avenues for drug discovery

EMBL Keynote Lecture: Chemical biology opens new avenues for drug discovery

Title history
  • EMBL Keynote Lecture: Chemical biology opens new avenues for drug discovery — observed on 20261101-0213 UTC (YouTube)

by Michelle Arkin · View the channel on PSI

Life & Natural Systems Biology PSBiology, life sciencesPSEChemical biology
🎙 Michelle Arkin 👥 16K 📅 September 22, 2026 ⏱ 53 min 👁 233 📄 expert opinion 🧭 2026-11-01
Available in: English (current) Français

Keywords

undruggablefragment-based drug discoverydisulfide tethering14-3-3KRAS

Summary

In this keynote lecture, Professor Michelle Arkin from UCSF discusses how chemical biology approaches are overcoming the ‘undruggable’ nature of many protein targets. She explains that undruggability often stems from the difficulty in finding ligands for protein-protein interactions (PPIs) rather than their biological importance. She presents two main strategies: fragment-based drug discovery and disulfide tethering. Fragment-based screening allows stepwise optimization of weak interactions, while disulfide tethering uses reversible covalent chemistry to stabilize binding. She illustrates these with examples including IL-2, KRAS, and the 14-3-3 protein, and introduces the concept of molecular glues to stabilize PPIs. The talk emphasizes the importance of cryptic pockets, dynamics, and the selective stabilization of specific complexes, particularly for intrinsically disordered proteins. She concludes by highlighting the potential for systematic discovery of selective stabilizers for 14-3-3 clients.

131 words

Critical Evaluation

Value of the Information & Strength of the Argument

The lecture provides a high-value overview of cutting-edge chemical biology methods, supported by specific case studies and structural data. The argumentation is solid, with logical progression from challenges to solutions, and she provides evidence for each claim, such as crystallographic structures and functional assays. She also discusses limitations and the need for future work, which enhances credibility.

Scientific Rigor, Source Quality, Title Accuracy

The talk references multiple published works, including the KRAS discovery by Shokat and Wells, and she presents her own research data. The title accurately describes the content. The scientific rigor is evident in the detail and quality of the presentation. No comments were provided for analysis.

118 words

Title / Content Match

The title precisely reflects the lecture's focus on chemical biology strategies for drug discovery, particularly targeting protein-protein interactions.

Quality & Reliability

9/10

Presentation by a recognized expert from a leading institution, with detailed structural and functional data. The talk is well-argued and consistent with current literature.

Key Moments

Markers derived by PSI from the transcript: the creator did not define chapters.

Cited Sources

  • Erlinson and Wells disulfide tethering technology — Mentioned as a key technology for reversible covalent fragment screening.
  • Shokat and Wells 2013 KRAS paper — Cited as demonstrating a cryptic site in KRAS using the same library.
  • IL-2 fragment linking study — Discussed as the first demonstration of fragment-based discovery for PPIs.

Contribution & Novelties

The talk offers a comprehensive synthesis of current approaches to targeting PPIs, emphasizing the role of dynamics and cryptic pockets. The original contribution lies in the articulation of undruggability 2.0, proposing molecular glues to stabilize native interactions, and the systematic use of disulfide tethering to discover selective stabilizers for 14-3-3 clients.

Pour aller plus loin :

99 words

Radar Profile

The score profile shows very high levels of technical depth, information quality, and fiability, with slightly lower quantity due to the focused scope. This is a highly specialized lecture with robust scientific content.

Reliability 9/10