Cleavable Linker
Cleavable linkers are critical structural components of antibody-drug conjugates (ADCs) that control intracellular payload release while maintaining systemic stability during circulation[1][2]. Mechanistically, cleavable linker systems exploit tumor-associated biochemical triggers, including lysosomal proteases, acidic intracellular compartments, and reducing cytosolic environments, to enable selective drug release within target cells[1][2][3]. Enzyme-sensitive peptide linkers, particularly valine-citrulline (Val-Cit) motifs, are extensively used because cathepsin-mediated cleavage efficiently liberates cytotoxic payloads after ADC internalization and lysosomal trafficking[2][3][4]. Disulfide-based cleavable linkers instead respond to elevated intracellular glutathione concentrations and redox imbalance in malignant cells, providing an alternative release mechanism for targeted drug delivery[1][2]. In cancer models, linker design directly influences pharmacokinetic stability, payload exposure, bystander activity, and therapeutic index, making linker selection a major determinant of ADC performance[1][2]. Compared with non-cleavable linkers, cleavable linkers can generate membrane-permeable payload species that extend cytotoxic activity beyond antigen-positive cells, although stability optimization remains essential to minimize premature release and off-target toxicity[2][3]. For experimental applications, ongoing linker engineering focuses on improving plasma stability while preserving efficient intracellular cleavage, supporting the development of next-generation targeted oncology therapeutics[1][4].
References:
- [1]. Xie J, et al. Can remdesivir and its parent nucleoside GS-441524 be potential oral drugs? An in vitro and in vivo DMPK assessment. Acta Pharm Sin B. 2021 Jun;11(6):1607-1616. [Content Brief]
- [2]. Bargh JD , et al. Cleavable linkers in antibody-drug conjugates. Chem Soc Rev. 2019 Aug 12;48(16):4361-4374. [Content Brief]
- [3]. Ashman N, et al. Non-internalising antibody-drug conjugates. Chem Soc Rev. 2022 Nov 14;51(22):9182-9202. [Content Brief]
- [4]. Merchán A, et al. Exploring Rigid and Flexible Scaffolds to Develop Potent Glucuronic Acid Glycodendrimers for Dengue Virus Inhibition. Bioconjug Chem. 2024 Jan 17;35(1):34-42. [Content Brief]
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Cleavable Linker Related Products (444)
Related Products (444)
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N-Boc-PEG7-alcohol
0 ImagesCat. No.: HY-130505CAS No.: 1292268-13-3N-Boc-PEG7-alcohol is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. N-Boc-PEG7-alcohol is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Azido-PEG5-CH2CO2H
0 ImagesAzido-PEG5-CH2CO2H is a cleavable 5 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG5-CH2CO2H is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG5-CH2CO2H is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
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m-PEG6-Amine
0 Imagesm-PEG6-Amine is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. m-PEG6-Amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG4-bis-PEG4-propargyl
0 ImagesCat. No.: HY-130973CAS No.: 2882973-11-5Mal-PEG4-bis-PEG4-propargyl is a cleavable 8 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Mal-PEG4-bis-PEG4-propargyl is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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BCN-SS-NHS
0 ImagesCat. No.: HY-135973CAS No.: 2751350-71-5BCN-SS-NHS is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). BCN-SS-NHS is a click chemistry reagent, it contains a BCN group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
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N-Boc-PEG6-alcohol
0 ImagesCat. No.: HY-W071584CAS No.: 331242-61-6N-Boc-PEG6-alcohol is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. N-Boc-PEG6-alcohol is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Me-triacetyl-β-D-glucopyranuronate-Ph-CH2OH-Fmoc
0 ImagesMe-triacetyl-β-D-glucopyranuronate-Ph-CH2OH-Fmoc is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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TCO-PEG1-Val-Cit-PABC-PNP TFA
0 ImagesCat. No.: HY-136100APurity: 99.69%TCO-PEG1-Val-Cit-PABC-PNP TFA is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). TCO-PEG1-Val-Cit-PABC-PNP TFA is a click chemistry reagent, which contains a TCO group that can undergo an inverse electron demand Diels-Alder reaction (iEDDA) with molecules containing Tetrazine groups.
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Gly-Gly-Gly-PEG4-methyltetrazine
0 ImagesGly-Gly-Gly-PEG4-methyltetrazine is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Gly-Gly-Gly-PEG4-methyltetrazine is a click chemistry reagent, it contains a Tetrazine group that can undergo an inverse electron demand Diels-Alder reaction (iEDDA) with molecules containing TCO groups.
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Propargyl-PEG2-NHBoc
0 ImagesCat. No.: HY-118808CAS No.: 869310-84-9Propargyl-PEG2-NHBoc is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG2-NHBoc is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG2-NHBoc is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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Biotin-C4-amide-C5-NH2
0 ImagesCat. No.: HY-W096148CAS No.: 151294-96-1Biotin-C4-amide-C5-NH2 is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG1-Val-Cit-PABC-OH
0 ImagesCat. No.: HY-130944CAS No.: 2055041-37-5Mal-PEG1-Val-Cit-PABC-OH is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Propargyl-PEG6-NHS ester
0 ImagesPropargyl-PEG6-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG6-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG6-NHS ester is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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PPC-NHS ester
0 ImagesSynonyms: 2,5-Dioxopyrrolidin-1-yl 3-(pyridin-2-yldisulfanyl)butanoatePPC-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Tetraethylene glycol monotosylate
0 ImagesCat. No.: HY-41541CAS No.: 77544-60-6Synonyms: Tos-PEG4Tetraethylene glycol monotosylate is a cleavable and acylhydrazone-based ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetraethylene glycol monotosylate also can be used as a PROTAC linker that can be used in the synthesis of PROTACs.
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Fmoc-Phe-Lys(Boc)-PAB-PNP
0 ImagesFmoc-Phe-Lys(Boc)-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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SNPB
0 ImagesSNPB is a cleavable linker that is used for making antibody-drug conjugate (ADC).
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Biotin-PEG3-aldehyde
0 ImagesCat. No.: HY-136051CAS No.: 889443-90-7Biotin-PEG3-aldehyde is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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AEEA-AEEA
0 ImagesAEEA-AEEA is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). AEEA-AEEA is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs.
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Mal-amido-PEG2-Val-Cit-PAB-PNP
0 ImagesMal-amido-PEG2-Val-Cit-PAB-PNP is a cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
