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]
-
Cleavable Linker Related Products (444)
Related Products (444)
-
SPP
0 ImagesCat. No.: HY-128926CAS No.: 341498-08-6Synonyms: N-succinimidyl 4-(2-pyridyldithio) pentanoateSPP (N-succinimidyl 4-(2-pyridyldithio) pentanoate) is a cleavable disulfide linker, can be used to form cytotoxic compound- linker conjugate.
-
Propargyl-PEG8-NHS ester
0 ImagesCat. No.: HY-130376CAS No.: 2182601-74-5Propargyl-PEG8-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Propargyl-PEG8-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG8-NHS 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.
-
Bis-PEG7-NHS ester
0 ImagesBis-PEG7-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG7-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Val-Cit
0 ImagesVal-Cit is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
β-Estradiol-6-CMO-PEG3-biotin
0 ImagesCat. No.: HY-130929β-Estradiol-6-CMO-PEG3-biotin is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
(2-pyridyldithio)-PEG1-hydrazine
0 Images(2-pyridyldithio)-PEG1-hydrazine is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Bromoacetamido-PEG4-acid
0 ImagesCat. No.: HY-141382CAS No.: 1807518-67-7Bromoacetamido-PEG4-acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Bromoacetamido-PEG4-acid is also a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Biotin-PEG4-PFP ester
0 ImagesCat. No.: HY-138488CAS No.: 1334172-58-5Biotin-PEG4-PFP ester is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
PC Biotin-PEG3-NHS ester
0 ImagesCat. No.: HY-140134CAS No.: 2353409-93-3PC Biotin-PEG3-NHS ester is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Propargyl-Tos
0 ImagesPropargyl-Tos is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-Tos is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
-
Bis-PEG8-acid
0 ImagesCat. No.: HY-126893CAS No.: 1246189-43-4Bis-PEG8-acid is a PEG-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG8-acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Bis-PEG10-NHS ester
0 ImagesCat. No.: HY-130824CAS No.: 2221949-02-4Bis-PEG10-NHS ester is a PEG/Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. Bis-PEG10-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Amino-Tri-(carboxyethoxymethyl)-methane
0 ImagesAmino-Tri-(carboxyethoxymethyl)-methane is a cleavable PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Amino-Tri-(carboxyethoxymethyl)-methan is also a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.
-
Mal-NH-ethyl-SS-propionic acid
0 ImagesMal-NH-ethyl-SS-propionic acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Fmoc-Gly-Gly-D-Phe-OH
0 ImagesFmoc-Gly-Gly-D-Phe-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Fmoc-Gly-Gly-D-Phe-OH is the D-isomer of Fmoc-Gly-Gly-Phe-OH (HY-131833).
-
Azide-PEG5-Tos
0 ImagesAzide-PEG5-Tos is a cleavable 5 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azide-PEG5-Tos 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.
-
N-Boc-diethanolamine
0 ImagesN-Boc-diethanolamine is an Alkyl/ether-based PROTAC linker can be used in the synthesis of PROTACs. N-Boc-diethanolamine is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
BCN-PEG1-Val-Cit-PABC-OH
0 ImagesCat. No.: HY-130923BCN-PEG1-Val-Cit-PABC-OH is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). BCN-PEG1-Val-Cit-PABC-OH is a click chemistry reagent, it contains a BCN group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
-
Mal-PEG2-Val-Cit-PABA-PNP
0 ImagesCat. No.: HY-131156CAS No.: 1345681-52-8Mal-PEG2-Val-Cit-PABA-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
DBCO-PEG3-SS-NHS ester
0 ImagesCat. No.: HY-133431DBCO-PEG3-SS-NHS ester is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG3-SS-NHS ester is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
