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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MP-PEG4-VK(Boc)G-OSu
0 ImagesCat. No.: HY-132163CAS No.: 2378428-21-6MP-PEG4-VK(Boc)G-OSu is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Ala-CO-amide-C4-Boc
0 ImagesCat. No.: HY-145367Ala-CO-amide-C4-Boc is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Propargyl-PEG1-SS-PEG1-PFP ester
0 ImagesCat. No.: HY-140110CAS No.: 1817735-30-0Propargyl-PEG1-SS-PEG1-PFP ester is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG1-SS-PEG1-PFP 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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LC-PEG8-SPDP
0 ImagesCat. No.: HY-126497CAS No.: 1252257-56-9LC-PEG8-SPDP is a cleavable ADC linker used for the antibody-drug conjugates (ADCs).
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DBCO-SS-aldehyde
0 ImagesCat. No.: HY-135977CAS No.: 2749492-45-1DBCO-SS-aldehyde is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-SS-aldehyde 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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Mal-PEG3-VCP-NB
0 ImagesCat. No.: HY-160982CAS No.: 1345681-77-7Mal-PEG3-VCP-NB (Compund 25c) is a degradable ADC linker containing a maleimide group, 3-unit PEG and VCP NB.
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Mc-Leu-Gly-Arg
0 ImagesCat. No.: HY-128927CAS No.: 2639874-49-8Mc-Leu-Gly-Arg is a cleavable ether linker for antibody-drug conjugates (ADC) design.
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DMAC-SPDB-sulfo
0 ImagesCat. No.: HY-131084CAS No.: 663599-07-3DMAC-SPDB-sulfo is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DBCO-PEG3-propionic EVCit-PAB
0 ImagesCat. No.: HY-136141DBCO-PEG3-propionic EVCit-PAB is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG3-propionic EVCit-PAB 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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SPDP-PEG12-acid
0 ImagesCat. No.: HY-141353SPDP-PEG12-acid is a cleavable 12 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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MC-Val-Cit-PAB-NH-C2-NH-Boc
0 ImagesCat. No.: HY-132973CAS No.: 1616727-22-0MC-Val-Cit-PAB-NH-C2-NH-Boc is a cathepsin cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Fmoc-Gly-Gly-D-Phe-OtBu
0 ImagesCat. No.: HY-44234AFmoc-Gly-Gly-D-Phe-OtBu is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-Gly-Gly-D-Phe-OtBu is the R-isomer of Fmoc-Gly-Gly-Phe-OtBu (HY-44234).
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Mal-PEG4-VA
0 ImagesCat. No.: HY-126669CAS No.: 1800456-31-8Mal-PEG4-VA is a cleavable ADC linker containing a Maleimide group. Mal-PEG4-VA is used for making antibody-drug conjugate.
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Fmoc-Ala-Ala-Asn(Trt)-OH
0 ImagesFmoc-Ala-Ala-Asn(Trt)-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Bis-PEG17-NHS ester
0 ImagesCat. No.: HY-130826CAS No.: 2221948-93-0Bis-PEG17-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG17-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Phe-Lys(Trt)-PAB
0 ImagesCat. No.: HY-129349CAS No.: 1116085-99-4Phe-Lys(Trt)-PAB is a cathepsin B substrate, and a cleavable ADC linker. Phe-Lys(Trt)-PAB acts as a lysosomally cleavable substrate for cysteine protease cathepsin B, with cleavage enabling linked anticancer drug release via self-immolative spacer . Phe-Lys(Trt)-PAB can be used for synthesis of ADCs.
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PAB-Ala-Val-CO-C2-mal
0 ImagesCat. No.: HY-179629CAS No.: 2279940-93-9PAB-Ala-Val-CO-C2-mal is a cleavable ADC linker, can be used for the synthesis of ADCs.
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TCO-PEG3-CH2-aldehyde
0 ImagesCat. No.: HY-136076TCO-PEG3-CH2-aldehyde is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). TCO-PEG3-CH2-aldehyde 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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DBCO-PEG4-Propionic-Val-Cit-PAB
0 ImagesCat. No.: HY-136103DBCO-PEG4-Propionic-Val-Cit-PAB is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG4-Propionic-Val-Cit-PAB 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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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.
