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 (445)
Related Products (445)
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Fmoc-Val-Ala-PAB-PNP
0 ImagesFmoc-Val-Ala-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Bis-PEG5-NHS ester
0 ImagesBis-PEG5-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG5-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DBCO-Sulfo-NHS ester sodium
0 ImagesCat. No.: HY-123687CAS No.: 1400191-52-7DBCO-Sulfo-NHS ester sodium is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-Sulfo-NHS ester (sodium) 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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Fmoc-NH-PEG8-CH2CH2COOH
0 ImagesFmoc-NH-PEG8-CH2CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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N-Boc-PEG1-bromide
0 ImagesCat. No.: HY-130503CAS No.: 164332-88-1N-Boc-PEG1-bromide is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. N-Boc-PEG1-bromide is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Fmoc-Gly-Gly-Phe-OH
0 ImagesFmoc-Gly-Gly-Phe-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Boc-Val-Cit-PAB-PNP
0 ImagesBoc-Val-Cit-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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MAC glucuronide linker-1
0 ImagesCat. No.: HY-44221CAS No.: 2222981-71-5MAC glucuronide linker-1 is a claevable ADC linker for antibody-agent-conjugations (ADCs).
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MC-Gly-Gly-Phe
0 ImagesMC-Gly-Gly-Phe is a cleavable linker used for antibody-drug conjugates (ADC).
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TCO-PEG3-Biotin
0 ImagesTCO-PEG3-Biotin is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). TCO-PEG3-Biotin 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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NH2-PEG4-CH2CH2COOH
0 ImagesNH2-PEG4-CH2CH2COOH is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). NH2-PEG4-CH2CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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MC-Gly-Gly-Phe-Gly
0 ImagesSynonyms: Mc-GGFG-OHMC-Gly-Gly-Phe-Gly is a cleavable ADC linker used for antibody-drug conjugates (ADCs).
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Boc-Val-Cit-OH
0 ImagesCat. No.: HY-W038702CAS No.: 870487-08-4Boc-Val-Cit-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DTSSP Crosslinker
0 ImagesCat. No.: HY-126349CAS No.: 81069-02-5DTSSP Crosslinker is a crosslinker reactive with primary amines. DTSSP Crosslinker is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Boc-Gly-Gly-Phe-Gly-OH
0 ImagesBoc-Gly-Gly-Phe-Gly-OH, a self-assembly of N- and C-protected tetrapeptide, is a protease cleavable linker used for the antibody-drug conjugate (ADC).
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MC-Val-Ala-PAB-PNP
0 ImagesMC-Val-Ala-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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N-Boc-PEG4-bromide
0 ImagesN-Boc-PEG4-bromide is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. N-Boc-PEG4-bromide is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Fmoc-NH-PEG2-CH2CH2COOH
0 ImagesFmoc-NH-PEG2-CH2CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-NH-PEG2-CH2CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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NH2-C5-PEG4-N3-L-Lysine-PEG3-N3
0 ImagesNH2-C5-PEG4-N3-L-Lysine-PEG3-N3 is a cleavable 7 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). NH2-C5-PEG4-N3-L-Lysine-PEG3-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-PEG4-CH2COOH
0 ImagesFmoc-NH-PEG4-CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-NH-PEG4-CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
