ADCs Linker

ADCs Linker

Catalog Product Name CAS Number Molecular Formula Molecular Weight
BADC-00542 4-Formyl-N-(2-(2-Methoxy-4-Methylphenoxy)ethyl)benzamide 1226006-54-7 C18H19NO4 313.35
BADC-00563 N-(2-(2-Ethylphenoxy)ethyl)-4-Formylbenzamide 1226394-63-3 C18H19NO3 297.35
BADC-00582 Fmoc-PEG4-NHS Ester 1314378-14-7 C30H36N2O10 584.61
BADC-00618 Mal-PEG4-VA 1800456-31-8 C26H42N4O11 586.63
BADC-00641 SPDMB 2101206-29-3 C14H16N2O4S2 340.42
BADC-00659 Propargyl-O-C1-amido-PEG4-C2-NHS ester 2101206-92-0 C20H30N2O10 458.46
BADC-00676 (2S,2'S)-Bis(2,5-dioxopyrrolidin-1-Yl) 4,4'-disulfanediylbis(2-(((benzyloxy)carbonyl)amino)butanoate) 299402-08-7 C32H34N4O12S2 730.76
BADC-00682 2,5-dioxopyrrolidin-1-yl 3-(4-hydroxyphenoxy)propanoate 616889-42-0 C13H13NO6 279.25
BADC-00684 EC089 625827-91-0 C36H46N14O14S 930.9
BADC-00366 N-SMP 55750-61-3 C10H8N2O6 252.18
BADC-00365 2,5-dioxopyrrolidin-1-yl 4-formylbenzoate 60444-78-2 C12H9NO5 247.20
BADC-00367 Mal-DPEG4-NHS 756525-99-2 C22H31N3O11 513.5
BADC-00368 N-[gamma-Maleimidobutyryloxy]sulfo-succinimide ester 158018-81-6 C12H12N2O9S 360.30
BADC-00503 SMCC 71875-81-5 C16H18N2O6 334.32
BADC-00712 SMCC 64987-85-5 C16H18N2O6 334.32
BADC-00372 SPDP 68181-17-9 C12H12N2O4S2 312.37
BADC-00506 GMBS 80307-12-6 C12H12N2O6 280.23
BADC-00597 Sulfo-SIAB sodium 144650-93-1 C13H10IN2NaO8S 504.19
BADC-00507 N-Hydroxysuccinimidyl-4-azidobenzoate 53053-08-0 C11H8N4O4 260.21
BADC-00501 Mc-Val-Cit-PABC-PNP 159857-81-5 C35H43N7O11 737.76

The antibodies, cytotoxic drugs, and linkers of ADC are the key elements in ADC design. The linker is a bridge between antibody and cytotoxic drugs. The ideal coupling must be stable in vitro or in the blood circulation to prevent systemic toxicity caused by the early release of cytotoxic drugs, and at the same time can enter and kill the cancer cells by quickly releasing effective cytotoxic drugs .

ADCs Linker

The linker should be stable enough in the circulation so that the payload stays connected to the antibody when it is distributed to the tissue (including solid tumor tissue). Once the ADC enters into the cancer cell, it can effectively release the drug with cytocidal activity . At present, ADC drugs use chemical covalent bonds (disulfide bonds, peptide bonds, thioether bonds, etc.) to achieve the connection between antibodies and chemical drugs. These linkers can be divided into " cleavable linker " and " noncleavable linker" based on their dissociation properties.

(1) Cleavable linker: The linker may be cleavable. Here, a chemical bond (or multiple chemical bonds) between the payload and the antibody attachment site (usually an amino acid) will be cleaved intracellularly. The cleavable linker can be degraded under different pH values or the action of intracellular enzymes to achieve the separation of chemical drugs from antibodies. Adcetris uses this kind of linker. Since the chemical may escape from the target cell after the drug is released, the drug can also kill the adjacent tissue of the target cell. (2) Noncleavable linker: The noncleavable linker maintains the coupling integrity of the antibody and the chemical drug throughout the entire drug action process. The final active metabolite, released by ADC in the lysosome after complete hydrolysis by the protease, contains the payloads and all the constituent elements of the linker still connected to the amino acid residues of the antibody, which is usually lysine or cysteine residue. Kadcyla uses this kind of non-cleavable linker, so the drug will eventually degrade into a mixture of amino acids, antibodies, chemicals and other components after entering the target cells.

At an appropriate concentration, the antibody conjugates with the drug. There are various coupling methods, which can be combined by strong covalent bonds, or by scattered ionic and hydrophobic bonds. For ADC drugs, it is necessary to ensure stability in aqueous solutions and facilitate use. According to different target cells, the connection mode suitable for each drug is selected through in vivo and in vitro experiments. The antibody-acanthomycin conjugate generally uses acid-sensitive hydrazone linkage, the antibody-maytansinol conjugate uses disulfide or thioether linkage, and the antibody-auristatin conjugate uses enzyme-digested peptides linkage or unbreakable thioethers linkage.

References:

  1. Gordon, M. , Canakci, M. , Li, L. , Zhuang, J. , Osborne, B. A. , & Thayumanavan, S. . (2015). A field guide to challenges and opportunities in antibody-drug conjugates for chemists. Bioconjug Chem.
  2. Polakis, & P. (2015). Antibody drug conjugates for cancer therapy. Pharmacological Reviews, 68(1), 3-19.
* Only for research. Not suitable for any diagnostic or therapeutic use.
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