Linker design could “make it or break it” when it comes to complex drug modalities like #PROTACs, #ADCs, bispecifics or #radioligands ???? The stakes are high. Consider Bristol Myers Squibb’s $4.1 billion acquisition of RayzeBio in , driven by the promise of its lead Phase 3 candidate, RYZ101, or Arvinas’ $1.01 billion agreement for a PROTAC androgen receptor degrader. These deals highlight that this is a highly sought-after space, where high risk comes with high reward. But the question remains: how can we de-risk the effort in the early pipeline? This is where precise chemical design becomes the foundation for success. Linkers are far more than molecular connectors—they are often the linchpin of a molecule’s performance, influencing stability, pharmacokinetics (PK), and payload delivery. ???? For #ADCs and peptide-drug conjugates, the right linker ensures a delicate balance—stability in circulation but precise release at the target site. Cleavable linkers, activated by the tumor microenvironment’s pH or enzymatic conditions, are a perfect example of how #chemistry delivers precision. ???? In #PROTACs, linkers play a pivotal role in aligning the E3 ligase with the target protein. This alignment is no small feat—it’s a delicate interplay of geometry, and getting it wrong can mean failure. ☢️ In #radiopharmaceuticals, linkers influence isotope distribution and half-life, directly impacting therapeutic efficacy and patient safety. ???? Even in chemical biology tools, modular linker designs are accelerating timelines by enabling more agile, streamlined discovery. Yet, designing these molecules comes with a unique challenge: new modalities often require longer synthetic sequences, leading to extended timelines for design and optimization. And this often means moving beyond simple PEG-based linkers to explore innovative alternatives that can better address the needs of stability, solubility, and payload delivery. This is precisely why advances in parallel synthesis and high-throughput approaches are so exciting. Our platform, Hercules+™, opens up new possibilities by enabling the rapid assembly of complex molecules and generating meaningful data for SAR and optimization. It is transforming the way we approach bottlenecks in design and synthesis, paving the way for faster, more informed decisions. As we continue to push the boundaries of what’s possible in modern drug discovery, collaboration and innovative thinking remain critical. Whether it’s stabilizing tricky molecules, mitigating risks like aggregation, or opening new IP opportunities, the right tools and expertise can turn complexity into opportunity. How are you approaching these challenges in your projects? I’d love to hear your thoughts. ???? Check out my previous post: https://bit.ly/3VlCIXQ ???? Or just DM and let’s explore options. #MedChem #Chemistry #MedicinalChemistry #DrugDiscovery #LinkerDesign #PharmaInnovation
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Dublin, May 19, (GLOBE NEWSWIRE) -- The "Targeted Protein Degradation by Novel PROTACs and Molecular Glues : A Landscape Analysis of Companies, Technologies, Targets, Investors and Partners From an Industry Perspective" report has been added to ResearchAndMarkets.com's offering.
This report provides you with a landscape description and analysis of Targeted Protein Degradation (TPD) technologies and of discovery and development of TPD drug candidates from an industry perspective as of May .
The report brings you up-to-date with information about and analysis of:
More than US$ 1.7 billion have been raised so far by TPD technology companies in financing rounds and from partnering deals. At the same time, nearly all major pharmaceutical companies have some kind of stake in the field of targeted protein degradation, with many of them pursuing in-house TPD technology development and TPD drug discovery.
This huge amount of money and the active role of major pharmaceutical companies highlight the tremendous interest from investors and major pharmaceutical companies and the opportunities they recognize in these new approaches to address previously considered undruggable targets with TPD small molecules.
The human proteome accounts for more than 30,000 proteins that have multiple biological functions in the human body. However, more than >80% of proteins are still out of reach and remain undruggable targets. Targeted protein degradation has recently emerged as a novel pharmacological modality that promises to overcome small molecule limitations whilst retaining their key advantages.
The PROTAC technology takes advantage of the ubiquitin-proteasome system to selectively degrade a protein of interest (POI). In brief, a PROTAC is a bifunctional heterodimer that binds simultaneously to a POI and to an ubiquitin E3 ligase, the two ends being linked together by a chemical tether. The close vicinity of the POI and the E3 ligase caused by the PROTAC triggers its ubiquitination.
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The tagged POI is then recognized and decomposed by the proteasome 26S, therefore freeing the PROTAC for further iterative cycles of degradation. Thus, only sub-stoichiometric amounts are needed for the potent activity. In comparison with a small-molecule inhibitor that requires high systemic exposure to sustain a pharmacological effect, the catalytic nature of PROTACs gives them the advantage to act effectively with a low systemic exposure, which is translated into reduced off-target problems and toxic side effects.
This report evaluates the industry landscape of targeted protein degradation with novel PROTAC and molecular glue technologies and compounds. The report is based on the identification and description of 20 major biopharmaceutical and 24 technology-focused companies with targeted protein degradation technologies and research and development activities.
For each company, a profile has been elaborated providing information about the company background/history, the financial situation, relevant technology, partnering deals and target and pipeline overview. Company profiles are presented in separate chapters for major pharmaceutical companies and technology-focused companies.
Provided that sufficiently detailed information was available, eight different targeted protein degradation technologies were described in more detail and their profiles are provided in the Chapter "Technology Profiles".
Eventually, this report has profiled ten drug candidates in preclinical and clinical stages of development. The descriptions can be found in the chapter "Drug Candidate Profiles" in alphabetical order by the drug code or generic name.
All information in the four chapters of Company Profiles, Technology Profiles and Drug Candidate Profiles are fully referenced with 78 scientific references, in many cases with hyperlinks leading to the source of information (abstracts, Posters, papers). Non-scientific references, such as press releases, annual reports or company presentations, are disclosed within the text with an embedded hyperlink leading to the online source of information.
Details about the collaboration and licensing agreements, acquisition terms as well as substantial financing rounds are described in the profiles of the TPD technology companies. The findings described in the four profile sections (Companies, Technologies, Drug Candidates) are summarized and analyzed in the chapter Description and Analysis.
What will you find in the report?
Key Topics Covered
Abbreviations
1 Executive Summary
2 Introduction & Overview
3 Description and Analysis
3.1 Characterization of Technology Companies
3.1.1 Key Features of Targeted Protein Degradation (TPD) Technologies
3.1.2 E3 Ligases & Linkers
3.1.3 Targets & Target Discovery
3.1.4 Pipeline of Targeted Protein Degraders
3.1.5 Financing & Partnering
3.2 Major Pharmaceutical Companies and Targeted Protein Degradation
3.2.1 TPD Drug Candidates in Development by Major Pharma Companies
3.2.2 Major Pharma's Internal TPD Activities
3.2.2.1 Resistance to TPD
3.2.2.2 Target Proteins
3.2.2.3 Discovery Approaches
3.2.2.4 Ligase Selection & Ligase Binders
3.2.2.5 Safety
3.2.2.6 Antibody-based Targeted Protein Degraders
3.2.2.7 PROTAC vs Molecular Glue Targeted Protein Degraders
4 Profiles of TPD Technology Companies
4.1 Amphista Therapeutics
4.2 Arvinas
4.3 BiotheryX
4.4 C4 Therapeutics
4.5 Captor Therapeutics
4.6 Cedilla Therapeutics
4.7 Cullgen
4.8 Dialectic Therapeutics
4.9 FIMECS
4.10 Hinova Pharmaceuticals
4.11 Kronos Bio
4.12 Kymera Therapeutics
4.13 Lycia Therapeutics
4.14 Monte Rosa Therapeutics
4.15 Nurix Therapeutics
4.16 Oncopia Therapeutics
4.17 Orionis Biosciences
4.18 Pin Therapeutics
4.19 Plexium
4.20 PolyProx Therapeutics
4.21 Sitryx Therapeutics
4.22 Trilo Therapeutics
4.23 Ubiquigent
4.24 Ubix Therapeutics
5 Profiles of Major Pharmaceutical Companies with Stakes in TPD
5.1 AbbVie
5.2 Amgen
5.3 AstraZeneca
5.4 Bayer
5.5 Biogen
5.6 Bristol-Myers Squibb (& Celgene)
5.7 Boehringer Ingelheim
5.8 Calico Life Sciences
5.9 Eisai
5.10 Eli Lilly
5.11 Gilead Sciences
5.12 GlaxoSmithKline
5.13 Janssen (Johnson & Johnson)
5.14 LEO Pharma
5.15 Merck
5.16 Novartis
5.17 Pfizer
5.18 Roche
5.19 Sanofi
5.20 Vertex Pharmaceuticals
6 Profiles of TPD Technologies
6.1 PROTAC Protein Degradation (Arvinas)
6.2 Daedalus Technology Platform (C4 Therapeutics)
6.3 DELPHe Platform (Plexium)
6.4 Pegasus Technology (Kymera)
6.5 Protein Degradation by Intrinsic Pathways (Cedilla Therapeutics)
6.6 Protein Hemostatic Modulators (BioTheryX)
6.7 Targeted Protein Modulation (Nurix Therapeutics)
6.8 uSMITE Technology (Cullgen)
7 Profiles of Drug Candidates
7.1 ARV-110
7.2 ARV-471
7.3 Avadomide
7.4 CC-
7.5 CC-
7.6 DT
7.7 Iberdomide
7.8 KYM-001
7.9 KYM-003
7.10 NRX
For more information about this report visit https://www.researchandmarkets.com/r/ugchkr
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