ADCs Linker

ADCs Linker

Catalog Product Name CAS Number Molecular Formula Molecular Weight
BADC-00971 MC-Gly-Gly-Phe-Gly-NH-CH2-O-CH2COOH 1599440-25-1 C28H36N6O10 616.62 g/mol
BADC-00889 m-PEG7-CH2COOH 1093647-41-6 C18H36O10 412.47 g/mol
BADC-00916 N-Boc-PEG7-alcohol 1292268-13-3 C19H39NO9 425.51 g/mol
BADC-00933 DBCO-NHS ester 1353016-71-3 C23H18N2O5 402.40 g/mol
BADC-01147 DSS Crosslinker 68528-80-3 C16H20N2O8 368.34 g/mol
BADC-01121 Amino-PEG6-alcohol 39160-70-8 C12H27NO6 281.35 g/mol
BADC-01144 NH2-PEG4-CH2CH2COOH 663921-15-1 C11H23NO6 265.30 g/mol
BADC-01138 5-Maleimidovaleric acid 57078-99-6 C9H11NO4 197.19 g/mol
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-00875 m-PEG6-SS-PEG6-methyl 1007386-15-3 C26H54O12S2 622.83 g/mol
BADC-00877 Aminooxy-PEG2-azide 1043426-13-6 C6H14N4O3 190.20 g/mol
BADC-00884 m-PEG8-Ms 1059588-19-0 C18H38O11S 462.55 g/mol

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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