In the past few years, Creative Biolabs has remained at the forefront of Antibody-Directed Enzyme Prodrug Therapy (ADEPT) development, we can deliver the highest quality services to our clients. To this end, we are excited to introduce our "ADEPT Pre-enzyme Drugs Design" service, which includes, but is not limited to, chemical synthesis of pre-enzyme drugs and analysis of their physicochemical properties. Our laboratory employs cutting-edge synthesis techniques to efficiently produce high-purity pre-enzyme drugs. Also, we are equipped to thoroughly evaluate essential characteristics of these drugs, such as solubility, stability, and lipophilicity.

Introduction

ADEPT is a targeted therapeutic approach designed specifically for certain cancer cells. It primarily utilizes antibodies to direct enzymes to the tumor site, facilitating the conversion of inactive drugs (prodrugs) into active compounds that possess anti-tumor properties. The effective execution of ADEPT largely hinges on the design of the proenzyme drug, which is the most crucial aspect of the process.

As a result, Creative Biolabs can offer highly customized prodrug molecule design, ensuring their biological activity in targeted cells while minimizing toxicity to healthy tissues. We develop molecular structures with enhanced specificity through methods such as chemical synthesis and modification. Moreover, our labs provide enzyme functionality optimization services for specific tumor cells, using protein engineering techniques to enhance the selectivity and specificity of enzymes in the tumor microenvironment. Moreover, we can assist clients in conducting stability research for enzymes, ensuring their activity and longevity in vivo.

Fig.1 Prodrug Design.^1,3

Services

Today, Creative Biolabs is proud to offer a comprehensive one-stop service for ADEPT pre-enzyme drug design, dedicated to helping clients achieve breakthroughs in the ADEPT field. Our service comprises two core components: drug chemical synthesis and physical-chemical property analysis, simplifying the complexities of the R&D process and delivering efficient, precise solutions.

Pre-enzyme Drug Chemical Synthesis Service

In our company, our drug chemical synthesis service is focused on providing tailored, efficient synthesis solutions for pre-enzyme drugs. By employing cutting-edge synthesis technologies and methodologies, we attain high-purity and high-yield target molecules. Our team of experts brings extensive experience in natural products and chemical synthesis, ensuring that the drugs synthesized meet the specific requirements for targeted therapies. We are dedicated to meticulous attention to detail, striving to shorten the R&D timeline while minimizing costs, ultimately offering our clients an exceptional service experience.

Physical and Chemical Property Analysis Service

At Creative Biolabs, thorough analysis of the physical-chemical properties of compounds is essential in drug development. Our physical-chemical property analysis service encompasses fundamental tests such as solubility, stability, and melting point, in addition to more detailed pharmacokinetic evaluations and structure-activity relationship analyses. Utilizing state-of-the-art analytical instruments and techniques, we provide clients with comprehensive, accurate reports that enhance compound optimization and improve the success rate of clinical applications. Our professional team collaborates closely with clients to deliver customized analysis solutions, ensuring the final products exhibit optimal safety and efficacy.

Fig.2 The Analysis of Gelation Tendency and Mechanical Properties.^2,3

Procedure

1. Selection and Optimization of Targeted Antibodies:

Initially, it is essential to select monoclonal antibodies that can specifically recognize antigens on the surface of tumor cells. These antibodies must undergo a rigorous selection and optimization process to enhance their affinity and specificity, ensuring effective binding to the tumor cells.

2. Enzyme Selection and Modification:

It is important to choose enzymes capable of activating prodrugs. Typically, enzymes with excellent catalytic activity and high specificity for the selected prodrugs are preferred. These enzymes can be derived from natural sources or modified through genetic engineering techniques to enhance their stability and catalytic efficiency in vivo.

3. Prodrug Design:

Prodrug molecules should be designed based on the characteristics of the target enzyme. Ideally, the prodrugs should exhibit low activity before enzyme activation to minimize toxicity to healthy tissues. Simultaneously, they need to be effectively activated by the enzyme after binding with the targeted antibody, leading to the release of drugs with anticancer properties.

4. Prodrugs Chemical Synthesis:

The chemical synthesis of prodrugs is a main step in the ADEPT technology pathway, involving several key processes:

a. Design and Optimization

In the early stages of synthesis, Creative Biolabs designs the structure of the prodrug based on the characteristics of the target tumor. Typically, computer-aided drug design (CADD) techniques are utilized to simulate the potential interactions between the drug molecule and the targeted antibody, optimizing its structure to enhance both activity and selectivity.

b. Selection of Synthetic Route

Choosing the appropriate chemical reaction pathway is crucial for the synthesis of prodrugs. Our staff assesses the molecular structure of the drug to identify suitable types of reactions (such as condensation, esterification, and reduction) and formulate a logical synthetic roadmap, ensuring the overall efficiency and reproducibility of the synthesis process.

c. Practical Synthesis

The practical synthesis involves procuring raw materials, optimizing reaction conditions (including temperature, pH, and reaction time), and separating and purifying the final product. Common techniques such as HPLC and Thin Layer Chromatography (TLC) are employed by our labs to ensure that the resulting prodrug maintains high purity and activity.

5. Physicochemical Properties Analysis

After completing the chemical synthesis, a comprehensive analysis of the physicochemical properties of the prodrug is essential to evaluate its biocompatibility and targeting capability.

a. Analysis of Physical Properties

Our analysis focuses on the physical characteristics of the prodrug, including solubility, stability, and melting point. Solubility assessments can be carried out under various pH conditions to ensure stable drug release in physiological environments.

b. Analysis of Chemical Properties

The examination of chemical properties involves evaluating the drug's chemical stability, reactivity, and degradation rates. In vitro experiments are conducted by us to study the chemical stability of the prodrug under different conditions, such as varying temperatures and pH levels.

6. Antibody-Enzyme-Prodrug System Construction

The optimized antibody is conjugated with the selected enzyme to create an antibody-enzyme complex. This complex can identify and bind to tumor cells in vivo, catalyzing the conversion of the prodrug into an active drug, thereby concentrating within the tumor microenvironment.

Advantages

• Enhanced Targeting: The design of proenzyme drugs can significantly improve drug targeting capabilities. By linking cell-specific antibodies to enzymes, proenzyme drugs can be activated within the tumor microenvironment, which helps minimize their effects on normal cells.
• Improved Bioavailability: Proenzyme drug design services contribute to enhanced bioavailability, ensuring that medications can accumulate effectively in tumor sites over an extended period.
• Flexible Enzyme Selection: Proenzyme drug design services provide an additional layer of assurance in enzyme selection. By carefully choosing enzymes with high specificity and low immunogenicity, the risk of immune reactions in patients can be reduced.

Creative Biolabs enhances the efficiency and precision of drug design, enabling clients to make significant advancements in the ADEPT field. Our chemical synthesis services are designed to deliver effective and accurate solutions for pre-enzyme drug synthesis. By conducting full analyses of physicochemical properties, clients can gain deeper insights into their drug performance, allowing them to develop more competitive research and development strategies. Our expert team is always ready to assist you, and we invite you to contact us anytime to learn more about our ADEPT pre-enzyme drug design services.

References

1. Nasibullin, Igor, et al. "Synthetic prodrug design enables biocatalytic activation in mice to elicit tumor growth suppression." Nature Communications 13.1 (2022): 39.
2. Coulter, Sophie M., et al. "In situ forming, enzyme-responsive peptoid-peptide hydrogels: An advanced long-acting injectable drug delivery system." Journal of the American Chemical Society 146.31 (2024): 21401-21
3. Distributed under Open Access license CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use