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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Boc-NH-ethyl-SS-propionic acid
0 ImagesCat. No.: HY-140116CAS No.: 485800-27-9Boc-NH-ethyl-SS-propionic acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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PTDA-PEG4-azide
0 ImagesSynonyms: PTAD-PEG4-N3PTAD-PEG4-N3 is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). PTAD-PEG4-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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Fmoc-NH-PEG5-CH2COOH
0 ImagesCat. No.: HY-133062CAS No.: 635287-26-2Fmoc-NH-PEG5-CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-NH-PEG5-CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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Bis-PEG9-acid
0 ImagesCat. No.: HY-126894CAS No.: 1268488-70-5Bis- PEG9- acid is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Bis- PEG9- acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG2-VCP-NB
0 ImagesMal-PEG2-VCP-NB is a claevable ADC linker containing a Maleimide group, 2-unit PEG and a VCP NB.
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Azido-PEG4-CH2-Boc
0 ImagesCat. No.: HY-42618CAS No.: 864681-04-9Azido-PEG4-CH2-Boc is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG4-CH2-Boc is also a PEG- and Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. Azido-PEG4-CH2-Boc 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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Mal-bis-PEG3-DBCO
0 ImagesMal-bis-PEG3-DBCO is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Mal-bis-PEG3-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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Tetrazine-PEG4-SS-NHS
0 ImagesCat. No.: HY-136040Tetrazine-PEG4-SS-NHS is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetrazine-PEG4-SS-NHS 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-NHCO-PEG4-amine
0 ImagesCat. No.: HY-124386CAS No.: 1255942-08-5
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Phe-Lys(Fmoc)-PAB
0 ImagesPhe-Lys(Fmoc)-PAB is a cathepsin cleavable ADC linker used for the antibody-drug conjugates (ADCs).
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Propargyl-PEG1-SS-PEG1-acid
0 ImagesCat. No.: HY-140109CAS No.: 1807503-85-0Propargyl-PEG1-SS-PEG1-acid is a cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG1-SS-PEG1-acid 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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Amino-PEG6-amido-bis-PEG5-N3
0 ImagesCat. No.: HY-130957Amino-PEG6-amido-bis-PEG5-N3 is a cleavable 11 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Amino-PEG6-amido-bis-PEG5-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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Mal-PEG2-bis-PEG3-BCN
0 ImagesCat. No.: HY-136060CAS No.: 2882973-13-7Mal-PEG2-bis-PEG3-BCN is a cleavable 5 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Mal-PEG2-bis-PEG3-BCN 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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Propargyl-PEG6-acid
0 ImagesCat. No.: HY-130386CAS No.: 1951438-84-8Propargyl-PEG6-acid is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG6-acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG6-acid 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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Fmoc-NH-PEG9-CH2CH2COOH
0 ImagesFmoc-NH-PEG9-CH2CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-NH-PEG9-CH2CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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m-PEG7-Amine
0 Imagesm-PEG7-Amine is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. m-PEG7-Amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Me-triacetyl-β-D-glucopyranuronate-Ph-ald-NO2
0 ImagesMe-triacetyl-β-D-glucopyranuronate-Ph-ald-NO2 is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Propargyl-PEG4-Tos
0 ImagesCat. No.: HY-130387CAS No.: 875770-32-4Propargyl-PEG4-Tos is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG4-Tos is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG4-Tos 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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Methyltetrazine-PEG4-SS-NHS ester
0 ImagesCat. No.: HY-133466CAS No.: 2656478-52-1Methyltetrazine-PEG4-SS-NHS ester is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Methyltetrazine-PEG4-SS-NHS ester 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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Mal-PEG1-Val-Cit-PAB-PNP
0 ImagesMal-PEG1-Val-Cit-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
