* Please be kindly noted that our services and products can only be used for research to organizations or companies and not intended for any clinical or individuals.

• PROTAC In Vivo Animal Model

The evaluation of drug effectiveness stands as a crucial step during drug development to assess if a drug will qualify for market release. The assessment of drug efficacy involves pharmacodynamic animal studies along with effectiveness research in clinical human trials. In vivo studies which offer definitive safety insights for PROTAC are essential for identifying the most promising PROTAC candidates for clinical testing. BOC Sciences focuses on in vivo evaluation research to support PROTAC discovery and development projects before clinical trials begin.

Our Available PROTAC In Vivo Evaluation Services

Pharmacodynamics Evaluation

Tumor Model Pharmacodynamics Evaluation: Research PROTAC drug effects on tumor growth by applying multiple tumor model systems including subcutaneous transplantation models, orthotopic transplantation models, and patient-derived xenograft (PDX) models. Researchers measure tumor volume and weight together with target protein degradation in tumor tissues.

Disease Model Pharmacodynamics Evaluation: Develop appropriate animal models for diseases including autoimmune and neurodegenerative conditions to examine PROTAC drug impacts on disease-specific indicators like inflammation factors and neuronal cell functioning.

Pharmacokinetic Research

Drug Metabolism and Kinetics Studies: Perform single and multiple dosing experiments across different species like mice, rats, dogs, and monkeys to track drug concentration variations in blood tissues and organs. Analyzing pharmacokinetic parameters including Cmax, AUC, t1/2, and CL helps in understanding how the drug undergoes absorption, distribution, metabolism, and excretion.

Drug Interaction Studies: Examine how PROTAC drugs interact with other medications through cytochrome P450 enzymes and drug transporters to determine their metabolic stability and drug interaction risks in vivo.

Safety Evaluation

Acute Toxicity Test: Expose animals to single doses of PROTAC drugs at multiple concentrations to study short-term toxic effects including behavioral changes and body weight alterations along with blood and biochemical parameter shifts in order to assess acute toxicity and lethal dosage levels.

Chronic Toxicity Test: Perform long-term toxicity assessments through repeated dosing to identify toxic responses in animals across extended durations like 28 days and 90 days. Assess how the drug affects animal growth and organ function along with tissue pathology.

Safety Pharmacology Studies: Study how PROTAC drugs impact vital physiological systems which include the central nervous system together with cardiovascular and respiratory systems. Therapeutic dose administration requires assessment of the drug's impact on vital system functions to maintain safety standards.

Mechanism of Action Studies

Protein Degradation Mechanism Studies: Perform in vivo examinations of how target proteins degrade by PROTAC drugs through their interactions with E3 ligases and during ubiquitination and proteasomal degradation to confirm the drug's mechanism of action.

Cell Signaling Pathway Studies: Explore how PROTAC drugs modify intracellular signaling pathways including MAPK, PI3K/Akt, and JAK-STAT to discover how these drugs regulate cell proliferation and apoptosis as well as cellular migration and various biological activities.

Drug Stability Studies

In Vivo Stability Studies: Understanding PROTAC drug stability in animal body environments involves examining drug degradation in blood and tissues and organs while studying metabolite generation and stability to enable drug formulation and dosing scheme development.

Drug Formulation Studies

Formulation Optimization Studies: Optimization studies should be performed on PROTAC drugs using their physicochemical properties and in vivo behavior to enhance drug solubility, stability, and bioavailability for better therapeutic efficacy and safety.

Route of Administration Studies: Assess how various administration methods including oral intake and intravenous or subcutaneous injections affect PROTAC drugs' in vivo pharmacodynamics and pharmacokinetics to determine optimal administration routes and dosages.

Why Choose Our Services?

Professional Team: An experienced team of scientists specializing in PROTAC technology research for many years, with a strong theoretical foundation and practical experience.

Advanced Experimental Facilities: Equipped with state-of-the-art laboratory equipment and instruments to ensure the accuracy and reliability of experimental data.

Diverse Model Options: Providing a wide range of tumor and disease models to meet various research needs.

Customized Services: Offering personalized experimental designs and data analysis plans based on customer needs.

Strict Quality Control: Adhering to international standards to ensure high-quality experimental processes and results.

Fast Response: Efficient service processes to ensure projects are completed on time.

Transparent Data: Providing detailed experimental reports and data to ensure customers have a comprehensive understanding of the experimental process and results.

Ongoing Support: Providing follow-up technical support and consultation services after the project concludes.

Workflow of PROTAC In Vivo Evaluation Service

1. Demand Analysis: Communicate with the client to understand specific needs and research objectives. Determine experimental models, experimental design, and expected outcomes.
2. Proposal Design: Develop a detailed experimental plan based on client needs. Provide a preview of the experimental plan and suggestions for modifications.
3. Contract Signing: After confirming the experimental plan, sign the service contract. Clarify service content, timelines, and costs.
4. Experiment Initiation: Prepare experimental materials and equipment according to the experimental plan. Perform preparatory work for the experiment, including establishing animal models and preparing the drugs.
5. Experiment Implementation: Carry out the experiment following the experimental plan. Collect and record experimental data regularly.
6. Data Analysis: Perform statistical analysis on the experimental data. Provide a detailed experimental report, including data charts and conclusions.
7. Result Delivery: Deliver the experimental report and data to the client. Provide interpretation and recommendations for the experimental results.
8. Follow-up Support: Provide follow-up technical support for the experimental results. Offer further research recommendations based on client needs.

Frequently Asked Questions (FAQs)

1. What studies are recommended for early-stage DMPK evaluation of PROTAC molecules?

This can generally be divided into two parts: one for characterizing the basic DMPK properties of the compounds, including physicochemical property determination, in vitro permeability testing, plasma protein binding, and preliminary in vitro drug interaction tests. The other part mainly focuses on further screening and optimization of the compounds, with an emphasis on solubility determination and in vitro metabolic properties (including both qualitative and quantitative studies). Selected compounds will then proceed to in vivo PK studies in rodents to further evaluate their DMPK properties.

2. How to choose an appropriate animal model for in vivo evaluation of PROTAC?

When selecting an animal model, factors such as disease relevance, drug metabolism characteristics, and species differences should be considered. For tumor studies, models such as subcutaneous tumor xenograft models, orthotopic tumor models, or patient-derived xenograft (PDX) models can be used. For neurodegenerative disease studies, corresponding transgenic or inducible animal models may be appropriate. Additionally, the availability, cost, and experimental cycle of the animal models should also be considered.

3. How to evaluate the in vivo efficacy of PROTAC drugs?

The in vivo efficacy of PROTAC drugs can be assessed through various methods, including measuring tumor volume, weight changes, survival rates, and other indicators. Changes in disease-related biomarkers, tissue histopathological alterations, and observations of animal behavior and physiological function can also be monitored. Furthermore, molecular biology techniques such as Western blotting and qPCR can be used to detect target protein degradation and related signaling pathway modulation.

4. How to assess the in vivo stability of PROTAC drugs?

The stability of PROTAC drugs can be evaluated through in vitro stability experiments under various conditions and by analyzing in vivo metabolites. In vitro stability experiments can involve exposing the drug to different pH levels, temperatures, and enzymes to observe degradation. In vivo metabolite analysis can utilize techniques like mass spectrometry to identify the types and structures of metabolites, assessing the drug's stability and metabolic pathways in the body.

References:

1. Guo, J., Liu, J., & Wei, W. (2019). Degrading proteins in animals:'Protac' tion goes in vivo. Cell research, 29(3), 179-180.
2. Kounde, C., Shchepinova, M. M., & Tate, E. (2019). A Caged E3 Ligase Ligand for Protac-Mediated Protein Degradation with Light. ChemRxiv. Preprint.

* PROTAC^® is a registered trademark of Arvinas Operations, Inc., and is used under license.