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XDC | Various New Drug Conjugates, In Addition to ADC, There Are More Choices.

With the continuous development of technology, the boundaries of drug conjugates are constantly expanding. Through the innovation of conjugated drug targets, antibodies, payloads and PEG linkers, and the updating of conjugation technology ( you can find Bioconjugation Service at AxisPharm) , a variety of new drug conjugates have emerged, such as :

Peptide Drug Conjugates (PDC),
Small Molecule Drug Conjugates (SMDC),
Radionuclide Drug Conjugates (RDC)
Antibody Immunostimulatory Drug Conjugates (ISAC),
Antibody Fragment Drug Conjugates (FDC),
Antibody Cell Conjugates (ACC),
Virus-like Drug Conjugates (VDC),
Antibody Oligonucleotide Conjugates (AOC),
Anti-Biopolymer Conjugates (ABC), etc.

XDC is a general term for various drug conjugates, consisting of targeting molecules, linkers, and cytotoxic drugs, where X is the carrier, D is the payload, and C is the conjugate.

By identifying tumor cells, they release the drug after endocytosis or directly in the tumor microenvironment (TME), thereby inducing microtubule inhibition, DNA damage and apoptosis, and also killing surrounding tumor cells through the bystander effect.

XDC’s “targeted molecule + drug conjugate” model can accurately identify and attack tumor cells, and can use fewer drugs to produce better therapeutic effects and lower toxicity.


 Radionuclide Drug Conjugates (RDC)

RDC consists of antibodies or small molecules, linkers, chelates, and cytotoxic/imaging factors (radioisotopes). RDC replaces small molecules with radionuclides. By achieving the purpose of precise radiotherapy, it kills tumors while reducing radiation to normal tissues, thereby reducing side effects. Commonly used for RDC include: antibodies, small molecules, peptides, etc. Radionuclides include: 68Ga, 64Cu for imaging diagnosis, and 177Lu, 213Bi, etc. for treatment.


At present, many companies are actively working on RDC development, and a number of radioactive therapies targeting PSMA are in the research and development stage.

Peptide Drug Conjugates (PDC)

PDC couples peptides to drug molecules to enhance the targeting of the drug, concentrate the drug on the target tissue, reduce its relative concentration in other tissues, and improve safety and effectiveness.

PDC integrates the advantages of polypeptides such as small molecular weight, biodegradability, and does not cause immunogenic reactions. It can modify the amino acid sequence of the peptide chain to change the conjugation hydrophobicity and ionization properties to solve problems such as poor water solubility and untimely metabolism.

PDC adopts HPLC (high performance liquid chromatography) technology, which is easy to purify and has advantages in production cost.

Antibody Fragment Drug Conjugates (FDC)

FDC consists of antibody fragments conjugated to cytotoxic drugs. Due to the small molecular weight of antibody fragments, FDC has better tumor penetration. The short half-life of FDC reduces its exposure in normal tissues and improves safety. The toxin/antibody fragment loading ratio (DAR), druggability, efficacy and safety of FDC can be better controlled by changing the chemical structure and length of the linker and adding PEG polymer to the conjugated drug.

Small Molecule Drug Conjugates (SMDC)

SMDC is composed of targeting molecules, connecting arms and effector molecules (cytotoxicity, E3 ligase). SMDC adopts small molecule orientation. The ligand of SMDC is highly selectively combined with transport proteins and is an organic functional group with a relatively small molecular weight.

Compared with antibody drugs, SMDC is easy to control the synthesis process and cost, and the industrial operation is simple.

SMDC theoretically does not produce immunogenicity and has good safety; in solid tumors, SMDC has good cell penetration and good in vitro and in vivo stability.

Currently, SMDC-related research has not yet made breakthrough progress. There are few active products in the SMDC pipeline and the target diversity is insufficient. No relevant products have been approved for marketing yet. The number of companies deploying this track is far lower than that of the ADC sector.

Immunostimulating Antibody Drug Conjugates (ISACs)

ISAC consists of a tumor-targeting monoclonal antibody coupled to an immune agonist through a non-cleavable linker. It can combine the precision of antibody targeting tumors and the killing potential of the innate and adaptive immune systems into a single drug. Achieve complete tumor regression and durable anti-tumor immunity in multiple tumor models.

Novel ISAC therapy has strong preclinical anti-tumor activity. ISAC’s representative drug BDC-1001 is currently in the clinical trial stage.

Antibody-Biopolymer Conjugates (ABC)

Antibody-Biopolymer conjugates (ABC) combine two or more drugs into one, thereby reducing costs and related side effects. Bispecific antibodies (can be understood as A antibody coupled to B antibody) , antibody-conjugated protein drugs, and antibody-conjugated nucleic acid drugs are the three common types of ABC.

Using its ABC technology platform, KODIAK is developing the anti-VEGF-macromolecule phosphorylcholine polymer conjugate KSI-301, which is currently in clinical trials. (Reference:

The drug is used to treat wet age-related macular degeneration, diabetic macular edema and retinal vein occlusion. By conjugating biopolymers with antibodies, the half-life of the drug in the eye can be extended, the frequency of injections can be greatly reduced, and the efficacy can be improved. ABC will also become a new coupling trend.

Virus-like Drug Conjugates (VDC)

VDC (Virus-like Drug Conjugate, VDC) is coupled to a potent cytotoxic drug that can be activated by infrared light. After activation, VDC generates high levels of singlet oxygen, selectively destroys tumor cells, and causes acute necrosis of tumor cells. , and at the same time, the death of immunogenic cells can activate the immune system to produce an anti-tumor response.

AU-011, a new virus-like drug conjugate (VDC) therapy launched by Aura Biosciences, is used to treat uveal melanoma and is currently in clinical trials. (Reference:

VDC is structurally complex, and both overall biological certainty and technological development are at an early stage.

Antibody-siRNA conjugate (ARC)

Small interfering RNA (siRNA) is also known as silencing RNA, short interfering RNA or non-coding RNA. The most critical step in siRNA is targeted delivery. Currently, there are three main strategies: chemical modification, biological conjugation and carrier-mediated vesicles.

As early as more than ten years ago, Harvard professor Judy Lieberman’s research group used antibody fusion to express protamine, and then used the positively charged protamine to load negatively charged siRNA. (Reference:

In 2015, Genentech Company used Thiomab technology to specifically couple and deliver siRNA. It was the first attempt to directly couple siRNA to an antibody. In a mouse tumor model, it showed intratumoral delivery and gene silencing effects. (Reference:

In response to various unfulfilled clinical needs, XDC specifically solves various challenges, including delivery problems (it is reported that ADC delivery efficiency is about 0.5%). According to relevant data, as of the end of last year, nearly 400 XDC drugs were in the clinical trial and marketing application stages around the world, and XDC will usher in a hundred flowers blooming.

AxisPharm offers Bioconjugation Service and a variety of ADC Linkers.


Read more about ADC articles:

ADC to XDC, Five Major Elements of Antibody Conjugate Drugs, Exploring the Fundamental Source of Innovation

ADC drug site-specific conjugation technology

Antibody-drug conjugates(ADCs) list Approved by FDA(2000-2024)

ADC drug for urothelial carcinoma( effective rate 81.6%)

ADC Linkers And Research Progress In Detail