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PROTAC Solutions

Proteolysis Targeting Chimeras (PROTACs) present significant opportunities in drug therapy, particularly where traditional small molecule inhibitors face challenges. By facilitating the degradation of proteins previously deemed “undruggable”, PROTAC broadens the scope of therapeutic targets, addressing unmet needs in conditions like cancer, neurodegenerative disorders, and genetic diseases. We can support the full scope of your PROTAC development program, from IND-enabling studies to NDA submission.

PROTAC Solutions Services by WuXi AppTec Lab Testing Division

IND Enabling Packages

In Vitro Studies

In Vivo Studies

Comprehensive Preclinical
Testing for PROTAC

We have more than 8 years’ experience in PROTAC research. We study 1,000+ PROTAC molecules every year and offer a variety of mature solutions and short experiment cycle. Our expert team, state-of-the-art facilities, and extensive services and capabilities support your PROTAC development program at every stage—including DMPK, bioanalytical, and pharmacology and toxicology testing—all through one, single-source partner.


We investigate the concentration-time profiles of PROTAC molecules in plasma and target tissues, providing critical data for dosing regimens and therapeutic efficacy.


We provide bioanalytical strategies designed to identify and execute the required assays for regulatory submission, placing your candidate on the most promising path.

Safety Assessment

We design and conduct comprehensive toxicology studies to evaluate the safety profile of PROTAC molecules, identifying risks and guiding dose selection for further development.


We support your CMC authoring needs, in both the US and China, from preclinical to commercial lifecycle management for both drug substance and product.


Get validated discovery assays, including in vitro assays and in vivo disease models in cardiovascular, CNS, respiratory, metabolic, and infectious diseases.

Regulatory Expertise

Make global filings convenient, efficient, and cost-effective across US FDA, NMPA, and EMA with our extensive regulatory submission support.

End-to-End Preclinical Services

We have facilitated the screening of tens of thousands of PROTAC molecules and supported the IND applications of dozens, leveraging our expertise in DMPK, bioanalysis, and safety assessment. Through this process, we have accumulated extensive experience and developed a distinctive preclinical evaluation system tailored specifically for PROTAC studies.

Global Partner & Network

WuXi AppTec is a true global provider in preclinical small and large molecule solutions, with state-of-the-art facilities and experts across US, Europe and China. We have decades of experience operating within diverse regulatory environments and delivering tailored testing solutions that advance ADCs from preclinical through IND, NDA and beyond.

Regulatory Expertise

We help you navigate the complex world of regulatory standards and guidance for PROTAC, bringing deep technical expertise enriched by constant interaction with regulatory authorities. This knowledge and detail is then translated into actionable, forward-looking testing strategies that meet stringent requirements and enable smooth progression from testing to regulatory approval.

Frequently Asked Questions

What are PROTACs?

PROTACs, or Proteolysis Targeting Chimeras, are a class of small molecule drugs designed to target and degrade specific proteins within cells. They are bifunctional molecules that induce the degradation of specific proteins by harnessing the cell’s natural ubiquitin-proteasome system. They consist of a ligand that binds to the target protein and another ligand that recruits an E3 ubiquitin ligase.

How do PROTACs work?

PROTACs function by bringing the target protein into close proximity with an E3 ubiquitin ligase, facilitating the ubiquitination of the target protein. This ubiquitinated protein is then recognized and degraded by the proteasome, effectively removing it from the cell.

Why is preclinical testing important for PROTACs?

Preclinical testing is important for advancing PROTACs, ensuring their safety, efficacy, and suitability for clinical translation. From a DMPK perspective, preclinical studies elucidate absorption, distribution, metabolism, and excretion profiles, vital for optimizing dosing regimens and addressing challenges such as poor bioavailability or metabolic instability. In Bioanalysis, rigorous assays are developed to accurately measure PROTAC levels in biological samples, overcoming challenges such as low concentrations or interference from endogenous molecules. Additionally, toxicity studies during preclinical testing are crucial for identifying potential adverse effects and mitigating challenges like off-target toxicities or immune reactions.

What are the unique challenges in preclinical testing of PROTACs compared to traditional small molecules?

The unique challenges in preclinical testing of PROTACs compared to traditional small molecules involve understanding factors affecting cellular uptake, stability optimization, and managing off-target effects. This includes evaluating membrane permeability, metabolic stability, and tissue distribution to enhance cellular penetration and minimize unintended interactions. Additionally, developing sensitive bioanalytical methods is crucial for quantifying PROTAC uptake, assessing stability, and detecting off-target interactions. Integration of these approaches facilitates PROTAC development, ensuring efficacy and safety for clinical trials.

What types of studies are essential in the preclinical testing of PROTACs?

In preclinical testing of PROTACs, essential studies include assessing cellular uptake to understand delivery efficiency, evaluating stability in biological environments to ensure sustained activity, investigating off-target interactions to mitigate unintended effects, characterizing pharmacokinetics to optimize dosing regimens, studying pharmacodynamics to elucidate mechanisms of action, assessing toxicity for safety assurance, and developing formulations for effective in vivo delivery. These studies address specific challenges unique to PROTACs, ensuring their efficacy, safety, and readiness for clinical trials.

How are the efficacy and mechanism of action of PROTACs evaluated preclinically?

Preclinically, the efficacy and mechanism of action of PROTACs are evaluated through specific methods tailored to their unique mechanism. One approach involves assessing target protein degradation in cell-based assays, where PROTAC-induced degradation is quantified using techniques such as Western blotting or immunofluorescence. Additionally, cellular assays measuring downstream effects on signaling pathways or cellular proliferation provide insights into the functional consequences of target protein degradation. Moreover, biochemical assays elucidate the binding affinity and kinetics of PROTACs to their target proteins and E3 ligases, helping to understand their mechanism of action at the molecular level.

What safety assessments are critical for preclinical testing of PROTACs?

Critical safety assessments for preclinical testing of PROTACs include a range of studies tailored to their unique mechanism of action. These include traditional toxicology studies to evaluate potential adverse effects on various organs, as well as specific investigations such as cardiotoxicity assessments due to potential off-target effects on cardiac proteins. Additionally, genotoxicity tests are essential to identify any DNA damage caused by PROTACs, ensuring their safety profile. Immunogenicity assessments play a crucial role in determining any immune response triggered by PROTACs, particularly considering their novel mechanism, which may elicit immune reactions.

How are the pharmacokinetics and pharmacodynamics of PROTACs studied in preclinical settings?

In preclinical settings, studying the pharmacokinetics (PK) and pharmacodynamics (PD) of PROTACs poses unique challenges. These include rapid degradation and potential metabolism by cellular enzymes, requiring sensitive analytical techniques to accurately quantify PROTAC concentrations. Additionally, assessing pharmacodynamics faces challenges due to intricate target protein degradation kinetics and downstream signaling modulation. Developing robust assays capable of capturing these dynamic processes is essential for elucidating their impact on cellular pathways.

What role do in vitro assays play in the preclinical testing of PROTACs?

In vitro assays are crucial for initial screening of PROTACs, assessing their ability to degrade target proteins, and evaluating cytotoxicity and off-target effects in different cell lines.

How are animal models used in the preclinical testing of PROTACs?

Animal models are used to study the in vivo efficacy, safety, and PK/PD profiles of PROTACs. These models help predict how PROTACs will behave in human subjects and identify potential therapeutic benefits and risks.

What are the regulatory considerations for preclinical testing of PROTACs?

Regulatory considerations include adhering to guidelines from agencies such as the FDA and EMA, conducting GLP-compliant toxicology studies, and ensuring comprehensive documentation of all preclinical findings to support an IND application.

How do you assess the stability and bioavailability of PROTACs in preclinical studies?

Stability is assessed through forced degradation studies and long-term stability testing under various conditions. Bioavailability is evaluated by measuring the concentration of PROTACs in plasma and tissues after administration.

What are the common toxicological studies performed for PROTACs?

Common toxicological studies include acute and chronic toxicity assessments, genotoxicity tests, reproductive toxicity studies, and carcinogenicity evaluations to identify potential adverse effects and establish safe dosing ranges.

How is the target selectivity of PROTACs evaluated preclinically?

Target selectivity is evaluated using biochemical assays and cell-based assays to confirm that the PROTAC selectively degrades the intended target protein without affecting other proteins significantly.

What are the potential off-target effects of PROTACs, and how are they assessed?

Potential off-target effects are assessed using proteomics approaches to identify unintended protein degradations and functional assays to monitor adverse cellular effects. These studies help minimize off-target toxicity.

How is the degradation efficacy of PROTACs measured in preclinical studies?

Degradation efficacy is measured using techniques such as Western blotting, immunoassays, and mass spectrometry to quantify the reduction of target protein levels in cells or tissues after treatment with the PROTAC.

What considerations are there for the design and optimization of PROTACs in preclinical research?

Considerations include optimizing the binding affinity of both ligands, ensuring linker stability and length, improving cell permeability, and minimizing off-target effects through selective E3 ligase recruitment.

What are the key components of a PROTAC that need to be tested preclinically?

Key components include the target-binding ligand, the E3 ligase-binding ligand, and the linker connecting them. Each component’s efficacy, stability, and safety must be evaluated individually and as part of the complete PROTAC.

How do linker design and drug conjugation affect the preclinical testing of PROTACs?

Linker design and drug conjugation impact the stability, specificity, and cell permeability of PROTACs. Effective linker design ensures optimal proximity between the target protein and E3 ligase, while appropriate drug conjugation enhances degradation efficacy and minimizes off-target effects.

Let’s Talk About Your PROTAC Program

Have questions? Need specific assays? Talk to an expert today about your PROTAC needs.