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PROTACs are providing a different way to modulate and treat a wide range of diseases through their ability to target protein degradation. A number of new players are actively engaged in harnessing the potential of PROTACs to create therapeutics with enhanced specificity and efficacy. This is helping to increase the tractability of previously challenging drug discovery targets.

PROTACs generally sit outside Lipinski space, their mechanism of action requiring larger molecular weights and distinct physicochemical properties (beyond the Rule of Five, Ro5). While these characteristics hold promise for novel drug modalities, they present challenges, particularly in terms of permeability and bioavailability. Having the ability to understand molecular profiles and characteristics as quickly and efficiently as possible is key to supporting profile improvement/optimization to reach candidate profiles as rapidly as possible.

Unveiling ChameLogK Assay for Enhanced Drug Discovery:

As we navigate the complexities of PROTAC molecule design, drawing from historical perspectives and contemporary advancements will contribute to a more comprehensive understanding and facilitate the development of optimized and effective therapeutics.

In this regard, chameleonicity, denoting a molecule’s ability to adapt to its environment through conformational changes, presents a strategic approach in medicinal chemistry. The optimization of solubility and permeability through the design of molecular chameleons is a key focus of this strategy.  

The ChameLogK paper unveils a descriptor of chameleonicity, demonstrating its effectiveness in evaluating 55 compounds, including those falling within or beyond Rule of Five (Ro5) boundaries. The paper showcases the assay’s utility in combination with lipophilicity (BRlogD) and polarity (Δ log kwIAM) descriptors, providing a comprehensive understanding of a compound’s profile. The inclusion of selected case studies, covering macrocycles, non-macrocyclic compounds, and PROTACs, further highlights the assay’s versatility and its role in property-based drug discovery strategies for designing bioavailable compounds beyond Ro5 constraints.

o2h Discovery is proud to disseminate the ChameLogK assay—a groundbreaking and cost-effective method for measuring chameleonicity, a vital factor in assessing PROTAC molecules’ potential. The assay, detailed in a paper accessible here (, offers a novel chromatographic descriptor with clear applications in drug discovery.

Chameleonicity for Protac Molecules

                       the above graph represents molecular weight vs ChamelogK values

We not only endorse the ChameLogK assay’s capabilities but have also validated its results at our end. This validation not only underscores the reliability of the assay but also demonstrates our dedication to providing our clients with trustworthy and impactful solutions.

In our comprehensive assay validation, PROTACs displayed a distinct “Chameleonic” quality. Macrocycles, led by Cyclosporin, demonstrated variable behaviour, while small molecules surprised with unexpected aggregation tendencies. E3 ligands exhibited consistent behaviour, possibly involving internal folding or interactions. Surprisingly, molecules like acetone, caffeine, and diazepam defied expectations. Phenol, despite its rigidity, showed a reproducible profile.

o2h discovery: First in the World to Offer the ChameLogK Assay to our Clients…

o2h discovery is thrilled to be the first in the world to offer the ChameLogK assay to our clients. With the capability to quickly and inexpensively measure chameleonicity, this assay represents a significant step forward in assessing PROTAC molecules and optimizing their properties. As we make this groundbreaking technology available, we invite our clients to explore the possibilities it presents in enhancing their drug discovery efforts. The ChameLogK assay, now a part of our service portfolio, positions our company at the forefront of innovation, providing clients with a valuable tool to navigate the complexities of molecule design in the ever-evolving landscape of drug development.

In addition to its groundbreaking applications in PROTAC research, the ChameLogK assay holds immense potential for advancing the development of novel therapeutics. By offering a rapid, and cost-effective means to measure chameleonicity, this assay opens new avenues for exploring compounds that were previously hindered by size-related challenges. As the industry navigates the complex terrain of drug discovery, our company stands ready to support clients in overcoming these hurdles and unlocking the full potential of their molecules.

Talk to Our Experts

Our off-the-shelf-toolbox for PROTAC Synthesis

Our team at o2h discovery has developed a rapid, cost-effective “off the shelf toolbox” with 100+ building blocks, with a range of E3 ligands (VHL and Lenalidomide) and ready-to-use linkers to couple with functionalized molecules of interest. These valuable resources facilitate the swift synthesis of PROTAC molecules, enabling the rapid assembly of degrader analogues for quick assembly of degrader analogues to jump start your drug discovery/development and PROTAC (degradation) programme. 

Chameleonicity for Protac Molecules

To know more about E3 ligase and linkers from our off-the-shelf-toolbox, or to talk to our expert to discuss your PROTAC programme, please reach out to us at

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