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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Fmoc-Phe-Lys(Trt)-PAB-PNP
0 ImagesFmoc-Phe-Lys(Trt)-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Aminoethyl-SS-propionic acid
0 ImagesCat. No.: HY-140096CAS No.: 15579-00-7Aminoethyl-SS-propionic acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DBCO-NHCO-PEG4-amine TFA
0 ImagesCat. No.: HY-124386A
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m-PEG11-Amine
0 ImagesCat. No.: HY-W040222CAS No.: 854601-60-8m-PEG11-Amino is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). m-PEG11-Amine is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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PEG4-SPDP
0 ImagesPEG4-SPDP is a cleavable ADC linker used for the antibody-drug conjugates (ADCs).
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Bis-SS-C3-NHS ester
0 ImagesBis-SS-C3-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG2-Val-Cit-PAB-OH
0 ImagesMal-PEG2-Val-Cit-PAB-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Mal-PEG2-Val-Cit-PAB-OH also can be used as a PROTAC linker that can be used in the synthesis of PROTACs.
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DBCO-PEG4-SS-TCO
0 ImagesCat. No.: HY-133432Purity: 99.9%DBCO-PEG4-SS-TCO is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG4-SS-TCO is a click chemistry reagent, it contains a TCO group that can undergo an inverse electron demand Diels-Alder reaction (iEDDA) with molecules containing Tetrazine groups.
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Amino-bis-PEG3-DBCO
0 ImagesCat. No.: HY-130972Amino-bis-PEG3-DBCO is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Amino-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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DBCO-NHCO-PEG4-NH-Boc
0 ImagesCat. No.: HY-126884CAS No.: 1255942-12-1DBCO-NHCO-PEG4-NH-Boc is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. DBCO-NHCO-PEG4-NH-Boc is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-NHCO-PEG4-NH-Boc 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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PC Alkyne-PEG4-NHS ester
0 ImagesCat. No.: HY-140139CAS No.: 1802907-98-7PC Alkyne-PEG4-NHS ester is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). PC Alkyne-PEG4-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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PC Mal-NHS carbonate ester
0 ImagesCat. No.: HY-140140CAS No.: 1408057-91-9PC Mal-NHS carbonate ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Azidoethyl-SS-ethylamine
0 ImagesAzidoethyl-SS-ethylamine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azidoethyl-SS-ethylamine 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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Tetrazine-SS-PEG4-Biotin
0 ImagesCat. No.: HY-136036Purity: 99.42%Tetrazine-SS-PEG4-Biotin is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetrazine-SS-PEG4-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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N3-PEG3-CH2CH2-Boc
0 ImagesCat. No.: HY-42489CAS No.: 252881-73-5N3-PEG3-CH2CH2-Boc is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). N3-PEG3-CH2CH2-Boc is also a PEG- and Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs. N3-PEG3-CH2CH2-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-amide-PEG4-Val-Cit-PAB-OH
0 ImagesMal-amide-PEG4-Val-Cit-PAB-OH is a cleavable ADC linker containing a Maleimide group. Mal-amide-PEG4-Val-Cit-PAB-OH is used in the synthesis of antibody-drug conjugates (ADCs).
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Fmoc-Hyp(Bom)-OH
0 ImagesFmoc-Hyp(Bom)-OH is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-Hyp(Bom)-OH is also a alkyl chain-based PROTAC linker that can be used in the synthesis of PROTACs<
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Propargyl-PEG7-acid
0 ImagesCat. No.: HY-130383CAS No.: 2093154-00-6Propargyl-PEG7-acid is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG7-acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG7-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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N-Boc-PEG9-alcohol
0 ImagesCat. No.: HY-W071583CAS No.: 2112731-44-7N-Boc-PEG9-alcohol is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. N-Boc-PEG9-alcohol is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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TCO-SS-amine
0 ImagesCat. No.: HY-136039CAS No.: 2918774-85-1TCO-SS-amine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). TCO-SS-amine is a click chemistry reagent, it contains a TCO group that can undergo an inverse electron demand Diels-Alder reaction (iEDDA) with molecules containing Tetrazine groups.
