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RNA Polymerase Inhibitors

RNA Polymerase Inhibitors

As a new generation of ADC payloads, RNA polymerase inhibitor toxins are paving the way for the treatment of refractory and drug-resistant tumors due to their unique transcription inhibition mechanism and potent cytotoxicity. BOC Sciences has been deeply engaged in the ADC field for years. Leveraging its robust synthesis platform, conjugation technologies, and analytical capabilities, we provide end-to-end services from custom synthesis of RNA polymerase inhibitor molecules to conjugate construction and analysis, assisting partners in advancing ADC candidates from concept to product.

Challenges of RNA Polymerase Inhibitors in ADC Applications

Comprehensive  Product Line

Limited Sources and Difficult Synthesis

RNA polymerase inhibitors are difficult to extract from natural sources and have complex structures. We offer efficient semi-synthesis and total synthesis processes to prepare high-purity α-Amanitin and its derivatives in bulk, supporting custom services from milligram to gram scale.

Competitive  Pricing

Strong Toxicity and Narrow Therapeutic Window

These toxins are highly potent, posing risks of systemic exposure. We enhance ADC safety and therapeutic index through linker screening and site-specific conjugation technologies to ensure toxin release specifically at the target site.

Flexible  Ordering Options

Few Conjugation Sites and Challenging Linkage Strategies

RNA polymerase inhibitors possess limited functional groups, posing conjugation difficulties. We have developed a variety of dedicated linker structures and modification techniques to achieve efficient and directional conjugation, ensuring ADC stability and activity.

Strict  Quality Control Testing

High Analytical Complexity and Quality Control Difficulty

The complex structure of the toxins makes analysis technically demanding. Our comprehensive analytical platform employs LC-MS/MS, SEC, HIC, and other methods to ensure accurate determination of structure, DAR, and purity.

RNA Polymerase Inhibitor Development Services

BOC Sciences offers one-stop development services for RNA polymerase inhibitor-based ADC payloads to pharmaceutical companies, research institutes, and ADC startups. Our services cover all stages from toxin synthesis, linker screening, conjugation strategy development, to analysis and scale-up manufacturing. Service modules include:

Molecular Customization and Structural Optimization

We provide the following custom services:

  • Extraction, purification, and semi-synthesis of natural α-Amanitin;
  • Structural modification of α-Amanitin derivatives (functional group introduction, solubility enhancement, etc.);
  • Structure modeling, SAR studies, and candidate screening based on customer designs;
  • Construction and comparative studies of Amanitin-like cyclic peptides.

Linker Strategy Design and Screening

Given the high polarity and complex structures of RNA polymerase inhibitors, linker strategies play a critical role in release control and toxicity regulation. We offer:

Payload Conjugation Process Development

By optimizing conjugation sites, controlling drug-to-antibody ratio (DAR), and improving grafting efficiency, we construct highly homogeneous conjugation systems:

  • Single-point or multi-point conjugation platforms (Lys, Cys, unnatural amino acids, etc.);
  • Fine-tuned control of conjugation conditions (solvent, temperature, pH);
  • Directional and stereoselective conjugation to prevent toxin leakage;
  • Conjugate preparation ranging from micrograms to grams.

Analytical Method Development and Purity Control

We possess complete analytical and quality evaluation capabilities to ensure the uniformity, safety, and traceability of each ADC batch:

  • Structural confirmation by LC-MS/MS;
  • DAR and purity determination by HIC, SEC, etc.;
  • RP-HPLC for monitoring free payload and linker stability;
  • In vitro enzymatic/acid degradation assays for release property evaluation;
  • Residual solvent and metal ion analysis.

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Comprehensive Capabilities for RNA Polymerase Inhibitor-Based ADCs

01

Extensive Experience in Toxin Synthesis and Modification

We have developed efficient synthesis and modification routes for dozens of natural product toxins, including cyclic peptides, glycosides, amides, flavonoids, and other complex structures, enabling both large-scale production and customization.

02

Diversified Linker Platform Resources

We have built a database of over 200 linker chemical scaffolds, allowing rapid screening of controlled-release strategies applicable to RNA polymerase inhibitors, with fast validation services available.

03

Efficient Conjugation and Scale-Up Capabilities

Our company is equipped with advanced bioconjugation facilities and a GMP-compatible pilot platform, enabling seamless transition from microgram-level studies to kilogram-scale production.

04

Comprehensive CMC Support System

We provide full lifecycle CMC technical support for ADC projects, covering structure identification, stability evaluation, formulation development, and quality standard establishment to ensure regulatory compliance of toxin-antibody products.

05

Multidisciplinary Expert Team Collaboration

Our team brings together expertise in organic chemistry, bioengineering, analytical sciences, and formulation development, enabling cross-disciplinary integration from structural design to functional validation.

06

Rapid Response and Customized Development Capability

With flexible project management and modular service systems, we respond quickly to client needs, offering highly customized services including toxin screening, structural modification, and conjugation strategy optimization.

End-to-End Workflow for RNA Polymerase Inhibitor Development

Scheme Design and Contract Customization

Project Requirement Communication and Technical Evaluation

We begin by engaging in in-depth communication with clients to understand their research goals and target characteristics. We clarify the direction of ADC construction, the required type of payload, and linker strategy. Meanwhile, we assess the suitability, safety, and development feasibility of RNA polymerase inhibitors, and formulate an initial project plan.

Payload/Linker Synthesis

Toxin Structure Design and Synthesis Development

Based on client needs or target characteristics, we provide natural α-Amanitin purification, derivative design, functional group introduction, and structural construction of novel RNA polymerase inhibitors. We support customized synthesis and structural optimization from milligram to gram scale.

Scheme Design and Contract Customization

Linker Screening and Attachment Construction

Taking into account the physicochemical properties of the payload and the desired release environment (e.g., pH, enzymes), we design and screen suitable linkers such as Cathepsin B-sensitive peptides, acid-labile bonds, or reducible disulfide bonds to ensure accurate release and stable delivery of the toxin in vivo.

Analysis, Purification and Characterization

Payload-Antibody Conjugation Strategy Development

According to the antibody type and linker structure, we develop the optimal conjugation strategy, control the drug-to-antibody ratio (DAR), maintain antibody activity, and improve conjugation efficiency and product uniformity to construct high-quality ADCs.

cGMP Manufacturing and Filling

Analytical Testing and Functional Validation

We use LC-MS/MS, HIC, SEC, and other analytical techniques for structure confirmation, DAR determination, purity analysis, and free toxin residue detection of ADCs. In vitro release tests and cytotoxicity pre-screening are also conducted to verify the effectiveness and stability of the constructed system.

Result Delivery

Pilot Scale-Up and Delivery Support

After experimental verification, BOC Sciences provides pilot-scale production services, establishing scale-up process parameters, batch consistency assessment, formulation stability testing, and delivering complete data packages to support client submission, transfer, or subsequent development.

Frequently Asked Questions

Frequently Asked Questions

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More About ADC Payloads

* Only for research. Not suitable for any diagnostic or therapeutic use.
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