Non-cleavable

Non-cleavable

Catalog Product Name CAS Number Molecular Formula Molecular Weight
BADC-00889 m-PEG7-CH2COOH 1093647-41-6 C18H36O10 412.47 g/mol
BADC-01147 DSS Crosslinker 68528-80-3 C16H20N2O8 368.34 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-00618 Mal-PEG4-VA 1800456-31-8 C26H42N4O11 586.63
BADC-00659 Propargyl-O-C1-amido-PEG4-C2-NHS ester 2101206-92-0 C20H30N2O10 458.46
BADC-00877 Aminooxy-PEG2-azide 1043426-13-6 C6H14N4O3 190.20 g/mol
BADC-00898 (R)-8-Azido-2-(Fmoc-amino)octanoic acid 1191429-18-1 C23H26N4O4 422.48 g/mol
BADC-00901 Azido-PEG9-amine 1207714-69-9 C20H42N4O9 482.57 g/mol
BADC-00902 Azido-PEG8-acid 1214319-92-2 C19H37N3O10 467.51 g/mol
BADC-00935 Biotin-PEG2-acid 1365655-89-5 C17H29N3O6S 403.49 g/mol
BADC-00948 DBCO-​C6-​acid 1425485-72-8 C21H19NO3 333.38 g/mol
BADC-00967 Propargyl-PEG5-amine 1589522-46-2 C13H25NO5 275.34 g/mol
BADC-00987 DOTA-​NHS-​ester 170908-81-3 C20H31N5O10 501.49 g/mol
BADC-01006 Bis-PEG1-PFP ester 1807539-02-1 C18H8F10O5 494.24 g/mol
BADC-01014 Propargyl-PEG2-acid 1859379-85-3 C8H12O4 172.18 g/mol
BADC-01028 Ald-Ph-amido-PEG4-propargyl 1969299-27-1 C19H25NO6 363.40 g/mol
BADC-01029 m-PEG12-amine 1977493-48-3 C25H53NO12 559.69 g/mol
BADC-01033 Fluorescein-DBCO 2054339-00-1 C39H27N3O6S 665.71 g/mol
BADC-01090 Boc-aminooxy-amide-PEG4-propargyl 2253965-01-2 C18H32N2O8 404.46 g/mol

BOC Sciences established advanced high throughput ADCs linkers production platform to meet the increasing demand for ADC linkers researches.

Antibody-drug conjugate (ADC) is a novel generation of antibody-targeted therapeutic drug, mainly applied for tumors and cancer treatment. Structurally, ADCs are composed of 3 components, the payload, antibody and linker. Mechanistically, ADCs act by binding to the target antigen on the cell surface, internalization via antigen-mediated endocytosis trafficking into the lysosome, and payload release through the proteolytic degradation of the antibody moiety/or cleavage of the linker. The rationale for developing ADCs is that linking a cytotoxic agent to a tumor-targeting antibody will enable selective targeting to cancer cells, leading to their eradication while sparing cells in normal tissues. Optimal ADCs achieving maximum efficacy with minimal toxicity require the appropriate combination of each of these components.

ADCs Linkers

Non-cleavableJ. Med. Chem. 2014, 57, 16, 6949–6964.

The most essential role of antibody-drug conjugates (ADCs) is the release of cytotoxic molecules in the cytoplasm, which is achieved by destroying the chemical linker between the antibody and the cytotoxic molecule. Thus, choosing a suitable linker is highly critical to ADCs. The ideal ADCs linker must satisfy the following conditions: it must be stable enough in the peripheral blood circulation to avoid the toxicity caused by the release of cytotoxic molecules. Thus, it can effectively release small cytotoxins after ADCs internalization. The key to ADCs therapeutic effect is to select a suitable linker and couple with the appropriate number of cytotoxins at the reaction site. The linkers can be divided into cleavable linkers and non-cleavable linkers based on their dissociation properties.

Non-cleavable Linkers

Non-cleavable linkers stabilized in the blood circulation system and tumor cells, such as thioethers linkers and amides linkers. After being engulfed by tumor cells, antibody-drug conjugates (ADCs) monoclonal antibodies (mAbs) are degraded in lysosomes, releasing small-molecule cytotoxic from the linker to exert antitumor effects. With this mechanism, differences between parent drugs and potential ADCs metabolites must be taken into consideration. For example, MMAE, a protein-based anti-mitotic drug, is most potent in its native form and is therefore poorly suited for derivatization with non-cleavable linkers. Conversely, MMAF retained its potency even when linked with a simple alkyl chain in vitro and in vivo. One proposed mechanism for the decreased efficacy of non-cleavable linked ADCs is that drugs bearing charged amino acids suffer from decreased membrane permeability, limiting their ability to kill nearby cells. Several non-cleavable alkyl and polymeric linkers have been explored in ADCs development. A notable example is the MCC amine-to-sulfhydryl bifunctional cross-linker featured in T-DM, this linker is especially useful as the cyclohexane ring provides a steric hindrance that decreases the hydrolysis of the resulting thioether.

References

  1. Jain, N.; et al. Current ADC Linker Chemistry. Pharm Res., 2015.
  2. Adair, J.R.; et al. Antibody-drug conjugates-a perfect synergy. Expert Opin. Biol. Ther., 2012, 12(9): 1191-1206.
* Only for research. Not suitable for any diagnostic or therapeutic use.

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