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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CL2 Linker
0 ImagesCat. No.: HY-128947CAS No.: 2270986-66-6CL2 Linker is a cleavableADC linker. CL2-SN-38 and CL2A-SN-38 are equivalent in agent substitution (~6), cell binding (Kd ~1.2 nM), cytotoxicity (IC50 ~2.2 nM), and serum stability in vitro (t1/2 ~20 hours).
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NO2-SPDMV-sulfo
0 ImagesCat. No.: HY-133549CAS No.: 663599-00-6NO2-SPDMV-sulfo is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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OPSS-Val-Cit-PAB-OH
0 ImagesCat. No.: HY-141144CAS No.: 3047198-15-9OPSS-Val-Cit-PAB-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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N-Boc-N-bis(PEG2-OH)
0 ImagesCat. No.: HY-117079CAS No.: 275385-03-0N-Boc-N-bis(PEG2-OH) is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. N-Boc-N-bis(PEG2-OH) is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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EC089
0 ImagesCat. No.: HY-128940CAS No.: 625827-91-0EC089 is a cleavable linker used in conjugates of tubulysins and folates, and extracted from patent WO2011069116A1.
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HyNic-PEG4-alkyne
0 ImagesCat. No.: HY-136075HyNic-PEG4-alkyne is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). HyNic-PEG4-alkyne 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-ethyl-SS-PEG3-NHBoc
0 ImagesCat. No.: HY-140099CAS No.: 2144777-87-5Amino-ethyl-SS-PEG3-NHBoc is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Aminoethyl-SS-ethylalcohol
0 ImagesCat. No.: HY-117409CAS No.: 15579-01-8Aminoethyl-SS-ethylalcohol is a glutathione cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Tetrazine-PEG5-SS-amine
0 ImagesCat. No.: HY-130945Tetrazine-PEG5-SS-amine is a cleavable 5 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetrazine-PEG5-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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Amino-PEG4-bis-PEG3-methyltetrazine
0 ImagesCat. No.: HY-130970Amino-PEG4-bis-PEG3-methyltetrazine is a cleavable 7 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Amino-PEG4-bis-PEG3-methyltetrazine 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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Methylcyclopropene-PEG3-amine
0 ImagesCat. No.: HY-136047CAS No.: 2749286-00-6Methylcyclopropene-PEG3-amine is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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THP-SS-alcohol
0 ImagesCat. No.: HY-140122CAS No.: 877864-04-5THP-SS-alcohol is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-C2-Gly3-EDA
0 ImagesCat. No.: HY-126673CAS No.: 2741725-04-0Mal-C2-Gly3-EDA is a cleavable ADC linker containing a Maleimide group. Mal-C2-Gly3-EDA is used for making antibody-drug conjugate.
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Boc-Val-Dil-Dap-Phe-OMe
0 ImagesCat. No.: HY-130975Boc-Val-Dil-Dap-Phe-OMe is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Bocaminooxyacetamide-PEG3-alkyne
0 ImagesCat. No.: HY-136101CAS No.: 2709738-66-7Bocaminooxyacetamide-PEG3-alkyne is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Bocaminooxyacetamide-PEG3-alkyne 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-aldehyde
0 ImagesCat. No.: HY-136074CAS No.: 2446160-72-9Methyltetrazine-PEG4-aldehyde is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Methyltetrazine-PEG4-aldehyde 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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Boc-aminooxy-ethyl-SS-propanol
0 ImagesCat. No.: HY-140117CAS No.: 2128735-21-5Boc-aminooxy-ethyl-SS-propanol is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DMAC-SPDB
0 ImagesCat. No.: HY-133550CAS No.: 663599-05-1DMAC-SPDB is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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PDdB-Pfp
0 ImagesCat. No.: HY-129372CAS No.: 2101206-44-2PDdB-Pfp is a cleavable ADC linker used for the agents that target for the extracellular loop 1 (ECL1) of TM4SF1 (transmembrane 4 L6 family member 1).
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SPDP-PEG36-NHS ester
0 ImagesCat. No.: HY-141358CAS No.: 2924873-20-9SPDP-PEG36-NHS ester is a cleavable 36 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
