Proximity inducing drugs offer transformative therapeutic opportunities by precisely controlling protein interactions and/or protein modulations including targeted protein degradation. PROTACs, prominent in this field, successfully degrade previously undruggable proteins like transcription factors by engaging both target proteins and E3 ligases. Despite their modular design however, PROTACs face challenges due to large molecular size, lipophilicity, poor bioavailability, and toxicity. Molecular glues present a promising alternative, overcoming these limitations with smaller size and improved bioavailability. Yet, identifying and optimizing glues is more challenging, as their binding interactions are still unpredictable. In this case study, Dr. Hans-Jörg Roth, former director at Novartis Global Discovery Chemistry, emphasizes optimizing cooperativity — boosting target affinity via chaperone proteins — as the key to developing smaller, highly selective, and safer proximity-inducing therapeutics.
Ready to tackle your challenging affinity screening?
Discover tools you can use
See more related content
18:36Many methods used in fragment-based drug discovery pose real challenges — SPR often struggles to detect true hits due to fragments’ small mass, DSF can have high rates of false positives, and NMR equi
14:18Transcription factors have traditionally been considered challenging therapeutic targets. Their intrinsic disorder and lack of small molecule binding pockets make them intractable to small molecule ap
Three things we took away from attending Drug Discovery Chemistry in 2024
Drug Discovery Chemistry is an annual event that focuses solely on early drug discovery, where scientists from around the world gather to showcase their research and participate in thoughtful...
12:54Dianthus is a biophysical screening instrument that uses Spectral Shift technology to measure molecular interactions for hit ID, hit-to-lead, and lead optimization. It offers a 384-well plate format a
11:48Applying Spectral Shift technology to study IDPs: Direct binding and displacement assays of MYC:MAX inhibitors
MYC is an important therapeutic target that associates with MAX to regulate gene transcription. Its lack of binding pockets and the presence of disordered regions make it a difficult protein to study
16:42How to keep your degrader pipeline moving forward with Dianthus
The development of your protein degrader is a multi-step and complex process usually packed with challenges that if left unsolved will delay the progress of your project. What if you could overcome co
22:23Selective degradation of cancer target WDR5 — Evaluation of PROTACs binary and ternary affinities with Spectral Shift
Chances are your company’s research and development pipeline includes several PROTAC candidates — placing you with many others in the race to bring successful and efficient protein degraders to the cl
37:25Put your challenging affinity screening campaigns back on track — after you’ve tried everything else
When you’re entrusted with developing therapeutics for challenging or undruggable targets, it’s a struggle to characterize molecular interactions. And it’s not for lack of effort or expertise — SPR an
NanoTemper Technologies launches Spectral Shift, a breakthrough technology that changes the game for affinity-based screenings
NanoTemper Technologies, announced today the launch of Spectral Shift technology within their Dianthus instrument, built to handle the most challenging affinity-based screenings in drug discovery....
10 terms to help you more easily understand targeted protein degradation
If you’re new to the world of TPD or you’re trying to keep up with all developments in this fast-moving field, here are some terms and definitions that will help you.
Use this downloadable list of 2023 Targeted Protein Degradation conferences to choose which one(s) to attend. Learn when and where they’ll happen, who’ll be there, and the main focus.
9 Targeted Protein Degradation conferences you don’t want to miss in 2022
With so much interest and investment in target protein degradation, a lot can happen in a year. Here are 9 conferences to get up-to-date on recent progress and the latest approaches. You’ll not...
Targeted protein degradation promises to lead the way to effective drugs for challenging targets