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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Acid-propionylamino-Val-Cit-OH
0 ImagesCat. No.: HY-130930CAS No.: 2098907-84-5Acid-propionylamino-Val-Cit-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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APN-PEG4-Amine (hydrochloride)
0 ImagesCat. No.: HY-130939CAS No.: 2748368-24-1APN-PEG4-Amine (hydrochloride) is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). APN-PEG4-Amine (hydrochloride) 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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Mal-PEG4-VC-PAB-DMEA TFA
0 ImagesCat. No.: HY-126668AMal-PEG4-VC-PAB-DMEA TFA is a degradable ADC linker containing a maleimide group and can be used to synthesize antibody conjugate active molecules (ADCs).
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Dimethylamine-SPDB
0 ImagesCat. No.: HY-133542CAS No.: 1193111-73-7Dimethylamine-SPDB is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DBCO-S-S-acid
0 ImagesCat. No.: HY-138506CAS No.: 2749426-25-1DBCO-S-S-acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-S-S-acid 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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Ala-Ala-Asn-PAB
0 ImagesCat. No.: HY-129360CAS No.: 2149584-00-7Ala-Ala-Asn-PAB is a peptide cleavable ADC linker for antibody-drug conjugates (ADCs).
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Fmoc-NH-ethyl-SS-propionic NHS ester
0 ImagesCat. No.: HY-140119CAS No.: 2128735-23-7Fmoc-NH-ethyl-SS-propionic NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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N-trifluoroacetyl-β-alanyl chloride
0 ImagesCat. No.: HY-138322CAS No.: 87639-76-7N-trifluoroacetyl-β-alanyl chloride is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DBCO-(PEG2-Val-Cit-PAB)2
0 ImagesCat. No.: HY-126676DBCO-(PEG2-Val-Cit-PAB)2 is a dual cleavable ADC linker for antibody-drug conjugates (ADCs). DBCO-(PEG2-Val-Cit-PAB)2 is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. DBCO-(PEG2-Val-Cit-PAB)2 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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Biotin-PEG4-SS-azide
0 ImagesCat. No.: HY-139107Biotin-PEG4-SS-azide is a cleavable, biotin-labeled, ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Biotin-PEG4-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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Diazo Biotin-PEG3-DBCO
0 ImagesCat. No.: HY-140930Diazo Biotin-PEG3-DBCO is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Diazo Biotin-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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2-Hydroxyethyl disulfide mono-tosylate
0 ImagesCat. No.: HY-140125CAS No.: 1807530-16-02-Hydroxyethyl disulfide mono-tosylate is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG4-bis-PEG3-methyltetrazine
0 ImagesCat. No.: HY-130953Mal-PEG4-bis-PEG3-methyltetrazine is a cleavable 7 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Mal-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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DMAC-PDB
0 ImagesCat. No.: HY-126531CAS No.: 663599-04-0DMAC-PDB is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal((3S,3aR,6S,6aR)-Hexahydrofuro[3,2-b]furan-3,6-diamine-PEG12)-β-Glu-PAB
![Mal((3S,3aR,6S,6aR)-Hexahydrofuro[3,2-b]furan-3,6-diamine-PEG12)-β-Glu-PAB](https://file.medchemexpress.com/product_pic/hy-173635.gif "Click to View Mal((3S,3aR,6S,6aR)-Hexahydrofuro[3,2-b]furan-3,6-diamine-PEG12)-β-Glu-PAB Product Detail")
0 ImagesCat. No.: HY-173635Mal((3S,3aR,6S,6aR)-Hexahydrofuro[3,2-b]furan-3,6-diamine-PEG12)-β-Glu-PAB is an interchain cysteines to a Maleimide-reactive, β-glucuronidase-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs), such as AZD0516 (HY-173639).
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Bis-SS-C3-sulfo-NHS ester
0 ImagesCat. No.: HY-133585CAS No.: 98604-89-8Bis-SS-C3-sulfo-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-amido-PEG9-Val-Ala-PAB-SG3200
0 ImagesCat. No.: HY-139956CAS No.: 1817788-75-2Mal-amido-PEG9-Val-Ala-PAB-SG3200 is a cleavable ADC linker conjugate used in the synthesis of antibody-drug conjugates (ADCs).
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AcLys-PABC-VC-Aur0101 intermediate-1
0 ImagesCat. No.: HY-48668CAS No.: 1609108-48-6AcLys-PABC-VC-Aur0101 intermediate-1 is a cathepsin cleavable ADC linker that is used for making antibody-drug conjugate.
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Aminooxy-PEG2-bis-PEG3-BCN
0 ImagesCat. No.: HY-136089Aminooxy-PEG2-bis-PEG3-BCN is a cleavable 5 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Aminooxy-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.
