Protein degraders show promising results in drug development pipelines. See progress candidates have made.

April 21, 2021 Patricia Piatti

There has been considerable and promising development in the field of targeted protein degradation (TPD) since the seminal discovery of PROTACs in 2001.¹ The appeal of degraders like PROTACs lies in their ability to resolve targets deemed “undruggable” by traditional inhibitor-based strategies.

We are now on the cusp of finally seeing TPD-based drugs in the clinic, as drug developers move to advance protein degraders within their pipelines. Arvinas LLC, for example, has two PROTAC® candidates that are now undergoing Phase 2 trials. One seeks to treat metastatic castration-resistant prostate cancer (mCRPC) by degrading the androgen receptor. Their other candidate aims to treat locally advanced or metastatic ER-positive/HER2-negative breast cancer by targeting the estrogen receptor. And, Kymera Therapeutics recently announced that their first PROTAC® to treat immuno-inflammatory diseases has entered a Phase 1 clinical trial. Their degrader candidate targets IRAK4, a key protein involved in inflammation mediated by the activation of TLRs and IL-1Rs.

A growing number of companies are also applying TPD strategies in other disease areas. Here are some examples of targeted diseases and where the protein degrader drug candidates stand in the company pipeline:

Cancer/Oncology:

Metastatic castration-resistant prostate cancer (mCRPC) – Phase 2²
ER+/HER2- breast cancer – Phase 2²
MYD88-mutant diffuse large B-cell lymphoma (DLBCL) – Preclinical³
STAT3-driven cancers – Preclinical³
Multiple myeloma & lymphoma – Clinical⁵
Synovial sarcoma & SMARCB1 deleted tumors – Preclinical⁵
B-cell malignancies – Preclinical²
KRAS-driven cancers – Preclinical²
Drug-resistant BRAF mutant melanoma and NSCLC – Discovery⁵
Drug-resistant RET-altered tumors – Discovery⁵
Drug-resistant EGFR+ NSCLC – Preclinical⁵
Other unspecified cancers^4,5,6,7

Neurodegenerative

Tau-driven neurodegeneration (FTLD-TAU, PSP, AD) – Preclinical²
Alpha synuclein-driven neurodegeneration (MSA, Parkinson’s) – Discovery²
mHTT-driven (Huntington’s) – Discovery²
Other unspecified neurodegenerative diseases⁴

Inflammatory and autoimmune disease

IL-1R/TLR pathway immune diseases – Phase 1³
Psoriasis and asthma – Preclinical⁴

Genetic Disorders

Cystic Fibrosis – Discovery⁴

In the coming months, we can expect to see more exciting breakthroughs in TPD in both the academic and clinical sectors. Learn how NanoTemper tools can help drive PROTAC technology from discovery to clinical development.

Sources:

How to build an effective protein degrader

Up next

Is your screening campaign stuck? 3 signs that it’s time to look for an alternative biophysical technology

If you work in a drug discovery lab, at some point, you too may realize that the technologies at hand are l...

Ready to tackle your challenging affinity screening?

Discover tools you can use

Learn more

Return to education center

Protein degraders show promising results in drug development pipelines. See progress candidates have made.

Cancer/Oncology:

Neurodegenerative

Inflammatory and autoimmune disease

Genetic Disorders

Previous

Up next

See more related content

Transcription 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

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...

Dianthus 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

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

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

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

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, announced today the launch of Spectral Shift technology within their Dianthus instrument, built to handle the most challenging affinity-based screenings in drug discovery....

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.

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...

One advantage of PROTACs is their unique mode of action — the induced proximity of an E3 ligase and the protein of interest (POI) triggers the ubiquitination and then degradation of the POI by the...