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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sulfo-SPDB
0 ImagesCat. No.: HY-101151CAS No.: 1193111-39-5sulfo-SPDB is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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N-Boc-PEG2-bromide
0 ImagesN-Boc-PEG2-bromide is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. N-Boc-PEG2-bromide is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG4-Val-Cit-PAB-PNP
0 ImagesMal-PEG4-Val-Cit-PAB-PNP is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DBCO-Val-Cit-PABC-PNP
0 ImagesCat. No.: HY-130937CAS No.: 2994332-18-0DBCO-Val-Cit-PABC-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-Val-Cit-PABC-PNP 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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Fmoc-NH-PEG3-CH2CH2COOH
0 ImagesFmoc-NH-PEG3-CH2CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-NH-PEG3-CH2CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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Biotin-PEG3-SS-azide
0 ImagesBiotin-PEG3-SS-azide is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Biotin-PEG3-SS-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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Boc-Dap-NE
0 ImagesBoc-Dap-NE is an intermediate in the synthesis of Monomethyl auristatin E (HY-15162), which is an inhibitor of tubulin polymerization. Monomethyl auristatin E can be used to synthesize Antibody-Drug Conjugates (ADCs) as ADC Cytotoxin.
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PDEC-NB
0 ImagesPDEC-NB is a disulfide cleavable linker used for the antibody-drug conjugate (ADC).
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Azido-PEG3-Val-Cit-PAB-PNP
0 ImagesAzido-PEG3-Val-Cit-PAB-PNP is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG3-Val-Cit-PAB-PNP is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG3-Val-Cit-PAB-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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Fmoc-Val-Ala-PAB-OH
0 ImagesFmoc-Val-Ala-PAB-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG1-NHS ester
0 ImagesMal-PEG1-NHS ester is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Mal-PEG1-NHS ester is PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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Cyclooctyne-O-NHS ester
0 ImagesCat. No.: HY-126517CAS No.: 1425803-45-7Cyclooctyne-O-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Cyclooctyne-O-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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Tetrazine-biotin
0 ImagesTetrazine-biotin is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetrazine-biotin 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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DBCO-PEG4-DBCO
0 ImagesCat. No.: HY-130346CAS No.: 2182601-68-7DBCO-PEG4-DBCO is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. DBCO-PEG4-DBCO is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG4-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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Mc-Val-Cit-PAB-Cl
0 ImagesCat. No.: HY-112099CAS No.: 1639351-92-0Mc-Val-Cit-PAB-Cl is a cleavable ADC linker. Mc-Val-Cit-PAB-Cl can be used to conjugate MMAE and antibody to form antibody-MC-vc-MMAE (e.g., anti-CD22-MC-VC-PABC-MMAE with IC50s of 3.3 and 0.95 nM for BJAB and WSU cell lines in cytotoxicity assay).
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PC Biotin-PEG3-azide
0 ImagesCat. No.: HY-140132CAS No.: 1937270-46-6PC Biotin-PEG3-azide is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). PC Biotin-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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endo-BCN-PEG4-acid
0 ImagesCat. No.: HY-135971CAS No.: 1881221-47-1endo-BCN-PEG4-acid is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). endo-BCN-PEG4-acid 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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Azido-PEG6-NHS ester
0 ImagesAzido-PEG6-NHS ester is a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG6-NHS ester is also a PEG- and Alkyl/ether based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG6-NHS ester 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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Azido-PEG3-SS-NHS
0 ImagesCat. No.: HY-135966CAS No.: 2446160-73-0Azido-PEG3-SS-NHS is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG3-SS-NHS 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.
