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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Bis-PEG13-NHS ester
0 ImagesBis-PEG13-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG13-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Boc-Val-Cit-PAB
0 ImagesBoc-Val-Cit-PAB is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Boc-NH-PEG6-CH2CH2COOH
0 ImagesCat. No.: HY-W040244CAS No.: 882847-13-4Boc-NH-PEG6-CH2CH2COOH is a cleavable ADC linker used as a linker for antibody-drug conjugates (ADC). Boc-NH-PEG6-CH2CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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MC-Val-Ala-OH
0 ImagesMC-Val-Ala-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Azide-C2-SS-C2-biotin
0 ImagesAzide-C2-SS-C2-biotin is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azide-C2-SS-C2-biotin 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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Br-PEG4-C2-Boc
0 ImagesBr-PEG4-C2-Boc is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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DBCO-Sulfo-Link-biotin
0 ImagesCat. No.: HY-130810CAS No.: 1363444-70-5DBCO-Sulfo-Link-biotin is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-Sulfo-Link-biotin 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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Methyltetrazine-Maleimide
0 ImagesCat. No.: HY-136104Purity: 98.12%Methyltetrazine-Maleimide is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Methyltetrazine-Maleimide 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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NHS-PEG2-SS-PEG2-NHS
0 ImagesCat. No.: HY-136133NHS-PEG2-SS-PEG2-NHS is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Tris[[2-(tert-butoxycarbonyl)ethoxy]methyl]methylamine
![Tris[[2-(tert-butoxycarbonyl)ethoxy]methyl]methylamine](https://file.medchemexpress.com/product_pic/hy-21577.gif "Click to View Tris[[2-(tert-butoxycarbonyl)ethoxy]methyl]methylamine Product Detail")
0 ImagesTris[[2-(tert-butoxycarbonyl)ethoxy]methyl]methylamine is a cleavable PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Amino-Tri-(t-butoxycarbonylethoxymethyl)-methane is also a PEG/Alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs.
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2-Aminoethyl-mono-amide-DOTA-tris(tBu ester)
0 Images2-Aminoethyl-mono-amide-DOTA-tris(tBu ester) is a metal chelator precursor containing a DOTA macrocyclic structure. DOTA can form highly stable complexes with metal ions (such as 68Ga, 177Lu) through four nitrogen atoms and four carboxylic acid groups to mediate targeted delivery of radionuclides. The tert-butyl ester group (tBu ester) of 2-Aminoethyl-mono-amide-DOTA-tris(tBu ester) also protects the carboxylic acid group during synthesis, and forms a free carboxyl group after deprotection reaction for coupling with targeting molecules (such as antibodies, peptides). 2-Aminoethyl-mono-amide-DOTA-tris(tBu ester) may be combined with tumor pre-targeting systems through bioorthogonal reactions (such as reverse electron demand Diels-Alder reaction) to study radioactive imaging or therapy of tumor tissues, and is mainly used in tumor pre-targeting research in the field of nuclear medicine.
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Boc-NH-PEG4-CH2COOH
0 ImagesCat. No.: HY-42640CAS No.: 876345-13-0Boc-NH-PEG4-CH2COOH is a cleavable ADC linker used as a linker for antibody-drug conjugates (ADC). Boc-NH-PEG4-CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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Fmoc-Ala-Ala-PAB
0 ImagesFmoc-Ala-Ala-PAB is a cleavable ADC linker. Fmoc-Ala-Ala-PAB can be used in the synthesis of antibody-drug conjugates (ADCs).
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Fmoc-NH-PEG8-CH2COOH
0 ImagesFmoc-NH-PEG8-CH2COOH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-NH-PEG8-CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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NH2-PEG6-CH2CH2COOH
0 ImagesCat. No.: HY-W040257CAS No.: 905954-28-1NH2-PEG6-CH2CH2COOH is a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). NH2-PEG6-CH2CH2COOH is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
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CL2A
0 ImagesCat. No.: HY-128945CAS No.: 2616704-22-2CL2A is a claevable complicated PEG8- and triazole-containing PABC-peptide-mc linker. CL2A is cleavable through pH sensitivity, giving rise to bystander effect, and binds the antibody at a cysteine residue via a disulfide bond. Labetuzumab govitecan used this linker.
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SPDB
0 ImagesSPDB is a glutathione cleavable ADC linker used for the antibody-drug conjugate (ADCs).
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TCO-PEG12-NHS ester
0 ImagesCat. No.: HY-141170CAS No.: 2185016-39-9TCO-PEG12-NHS ester is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. TCO-PEG12-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Fmoc-Glu-(Boc)-Val-Cit-PAB-PNP
0 ImagesCat. No.: HY-136154Fmoc-Glu-(Boc)-Val-Cit-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-VC-PAB-PNP
0 ImagesMal-VC-PAB-PNP is a cleavable ADC linker. Mal-VC-PAB-PNP can be used in the synthesis of antibody-drug conjugates (ADCs).
