ADC Conjugation

Antibody-drug conjugate (ADC) development is a multidimensional scientific challenge. Success depends  on the specificity of the antibody, the stability of the linker, and the potency of the payload, and—most critically—the precision of the conjugation process, enabling synergy among these three components.

Typical conjugation approaches include non-site-specific and site-specific conjugation technologies, each offering distinct advantages and challenges. These techniques influence the control over drug-to-antibody ratio (DAR) uniformity, conjugation efficiency, and the overall pharmacokinetic/pharmacodynamic (PK/PD) profile of the ADC.

ChemExpress offers a versatile and expandable conjugation platform that extends beyond ADCs, supporting multiple conjugated modalities such as DACs, APCs, FDCs, and AOCs to address diverse drug development strategies and next-generation therapeutic.

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One-Stop ADC
CDMO Service

ChemExpress offers integrated services spanning from Payload-Linker to ADC DS&DP, enabling efficient scale-up and seamless technology transfer, effectively reducing management and transition costs.

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Extensive Project Experience
& Comprehensive Inventory

Over 80 CMC projects, 6 BLA projects, and 1 commercial project have been delivered. 16 ADC payloads and related intermediates are registered with the FDA as DMFs.

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Expert Scientific
Team

Our team of over 700 scientists provides comprehensive support from R&D to commercialization, ensuring high-quality, scalable solutions for your ADC pipeline.

Our Services

ChemExpress tailors conjugation technologies to your specific molecule, providing end-to-end ADC conjugation services — from conjugate sample preparation and process optimization to stability studies — accelerating your path toward successful ADC and other XDC modalities development.

Our Service Scope Includes

  • Site-specific & Non-site-specific Bioconjugation Technologies: Cysteine-based conjugations (-SH), Lysine-based conjugations (-NH2), N-Glycan Conjugations and Enzyme conjugations
  • Bispecific Antibody-Drug Conjugate (BsADCs),Tri-specific Antibody-Drug Conjugate (Tri-ADC), etc.
  • Dual Payload Conjugation
  • Conjugate Sample Preparation
  • Conjugation Process Development and Optimization
  • Conjugation Process Characterization
  • Stability Studies

How to choose the right conjugation strategy for your Antibody Drug Conjugation development?

Fig.1 The characteristics of various conjugation methods applied for ADC
Conjugation methods Schematic diagram Advantages
Non-site
specific
conjugation
Lysine sites • Rapid and convenient
Reduced
cysteine sites
• A relatively homogeneous product
Site-specific
conjugation
Engineered reactive
cysteine residues
• High homogeneity;
•Tunable reactivity and stability
Disulfide
re-bridging
• High homogeneity;
•No influence on spatial structure of antibody;
•National amino acid sequence and glycosylation
Unnatural
amino acids
•High homogeneity;
•Tunable reactivity and stability;
•High efficiency of conjugation
Enzyme-assisted
ligation
•High homogeneity;
•High efficiency of conjugation
•DAR alteration possible
Glycan
remodeling and
glycoconjugation
•High homogeneity;
•No alteration of amino acid sequence
pClick technology •Without antibody engineering or chemical / enzymatic treatments
•Simple, efficient, and convenient

Why Partner with ChemExpress

Extensive Experience

With extensive expertise in innovative conjugation technologies, our service covers bispecific antibody conjugation (BsADCs), dual-payload conjugation, and other advanced modalities, and we successfully completed over 500 conjugation projects

Precise Control

Customized DAR distribution, with precise control (2.0/4.0/8.0±0.3) and >98% monomer purity (SEC-HPLC verified), ensuring high-quality and reproducible results

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Versatile Conjugation Solutions

Comprehensive conjugation solutions for cysteine-based conjugations (-SH), lysine-based conjugations (-NH2), N-glycan conjugation and enzyme-mediated conjugations, supporting both non-site-specific and site-specific technologies, offering tailored solutions for diverse needs, such as DAR and free payload quality control, etc

Different Scales of Conjugation Reactors

Equipped with 5L, 20L, 50 L, 100 L, 200 L and 500 L conjugation reactors to meet diverse conjugation scale requirements, with cross-scale performance stability validated for seamless process transfer

Our Sites

R&D & Manufacturing Sites

研发1
Shanghai Headquarter R&D Center
ADC Conjugation Customized Synthesis
研发2
Chongqing ADC CDMO Manufacturing Site
XDC Research, Process Development and Manufacturing

Case Study

ADC Sample Preparation – Bridged Cysteine Conjugation

ADC Sample Preparation – Bridged Cysteine Conjugation This study evaluated the applicability and consistency of bridged cysteine conjugation technology across different antibody systems.
Three different antibodies were conjugated using the same payload-linker system. Mass spectrometry analysis showed DAR values around 4, while the DAR distribution varied slightly among the different antibody scaffolds.
By optimizing conjugation parameters—including reductant equivalents, reaction time, and pH—ChemExpress improved the proportion of the DAR4 species, achieving a more uniform DAR distribution, providing a robust foundation for scale-up and platform process development.

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FAQs

ChemExpress requires approximately 10 mg of antibody as the minimum starting material for a custom ADC conjugation request. All ADC samples delivered by ChemExpress undergo sterile filtration and endotoxin removal, ensuring that the final material meets sterility and low-endotoxin requirements.

· Based on the molecular weight difference between the payload linker and the antibody, purification methods such as ultrafiltration and size exclusion chromatography (SEC) can be leveraged for removal.
· When using site-specific conjugation techniques such as enzymatic conjugation or N-glycan conjugation, enzymes can be removed through purification processes like affinity chromatography.
· Based on differences in charge distribution and hydrophobicity, impurities can be removed using purification processes such as cation exchange chromatography (CEX), anion exchange chromatography (AEX), and hydrophobic interaction chromatography (HIC).

The thioether bond formed between maleimide and thiol groups may undergo retro-Michael addition in the presence of exogenous thiol-containing molecules, such as cysteine on serum albumin and glutathione (GSH). This instability may compromise the circulatory stability of the drug, increase off-target toxicity, and reduce the therapeutic efficacy of ADCs.
Solutions: Hydrolytic ring-opening or modifying the payload-linker (PL) by incorporating PEG or other modifications.

ChemExpress provide an integrated analytical platform including HIC, SEC-MS, LC–MS, and UV/Vis spectroscopy for DAR value, conjugation site identification, payload distribution analysis, free drug quantification, and residual impurities analysis. Method development and qualification are performed in alignment with ICH and FDA/EMA guidelines.

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