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 (445)
Related Products (445)
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Azide-C2-Azide
0 ImagesAzide-C2-Azide is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azide-C2-Azide 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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SC-Val-Cit-PAB
0 ImagesCat. No.: HY-126667CAS No.: 2922649-64-5SC-Val-Cit-PAB is a cleavable ADC linker for antibody-drug conjugates (ADCs).
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Boc-amino-PEG3-SS-acid
0 ImagesCat. No.: HY-136037Boc-amino-PEG3-SS-acid is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Amino-PEG4-bis-PEG3-N3
0 ImagesCat. No.: HY-136090CAS No.: 2758876-18-3Amino-PEG4-bis-PEG3-N3 is a cleavable 7 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Amino-PEG4-bis-PEG3-N3 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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(2-Pyridyldithio)-PEG6 acid
0 ImagesCat. No.: HY-1320862-Pyridyldithio-PEG6 acid is a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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PC-Biotin-PEG4-PEG3-azide
0 ImagesCat. No.: HY-140133CAS No.: 2055198-04-2PC-Biotin-PEG4-PEG3-azide is a cleavable 7 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). PC-Biotin-PEG4-PEG3-azide 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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Methyltetrazine-PEG4-oxyamine
0 ImagesCat. No.: HY-136056Methyltetrazine-PEG4-oxyamine is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Methyltetrazine-PEG4-oxyamine 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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Tetrazine-PEG4-SS-Py
0 ImagesCat. No.: HY-130947Tetrazine-PEG4-SS-Py is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetrazine-PEG4-SS-Py 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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Ald-Ph-PEG4-bis-PEG3-N3
0 ImagesCat. No.: HY-130969Ald-Ph-PEG4-bis-PEG3-N3 is a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Ald-Ph-PEG4-bis-PEG3-N3 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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Biotin-PEG2-methyl ethanethioate
0 ImagesCat. No.: HY-138508Biotin-PEG2-methyl ethanethioate is a cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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N-Succinimidyl 3-(Bromoacetamido)propionate
0 ImagesCat. No.: HY-141385CAS No.: 57159-62-3Synonyms: 3-(2-Bromoacetamido)propanoic acid NHS esterN-Succinimidyl 3-(Bromoacetamido)propionate is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. N-Succinimidyl 3-(Bromoacetamido)propionate is also a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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4-Methyl-4-(pyridin-2-yldisulfanyl)pentanoic acid
0 ImagesCat. No.: HY-133409CAS No.: 1537891-69-24-Methyl-4-(pyridin-2-yldisulfanyl)pentanoic acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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PC DBCO-PEG3-biotin
0 ImagesCat. No.: HY-140136PC DBCO-PEG3-biotin is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). PC DBCO-PEG3-biotin is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
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Azido-PEG1-Val-Cit-PABC-PNP
0 ImagesCat. No.: HY-136105Azido-PEG1-Val-Cit-PABC-PNP is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG1-Val-Cit-PABC-PNP 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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Hydroxy-PEG3-SS-PEG3-alcohol
0 ImagesHydroxy-PEG3-SS-PEG3-alcohol is also a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG1-Val-Cit-OH
0 ImagesCat. No.: HY-133459Mal-PEG1-Val-Cit-OH is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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NH2-PEG4-hydrazone-DBCO
0 ImagesCat. No.: HY-136131NH2-PEG4-hydrazone-DBCO is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). NH2-PEG4-hydrazone-DBCO is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
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DBCO-NHCO-PEG4-acid
0 ImagesCat. No.: HY-125541CAS No.: 1870899-46-9DBCO-Amide-PEG5-acid is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. DBCO-Amide-PEG5-acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-NHCO-PEG4-acid is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
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Tetrazine-Ph-SS-amine
0 ImagesCat. No.: HY-133504Tetrazine-Ph-SS-amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetrazine-Ph-SS-amine 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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Ald-Ph-amido-PEG23-OPSS
0 ImagesCat. No.: HY-130962Ald-Ph-amido-PEG23-OPSS is a cleavable 23 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
