Disulfide Cleavable Linker
Disulfide cleavable linkers provide redox-responsive bonds for drug delivery because extracellular and intracellular glutathione gradients enable selective activation in reductive cytoplasmic environments[1]. Mechanistically, disulfide cleavage can release small-molecule drugs, macromolecule conjugates, or masked bioactive agents after cellular entry[2][3]. In cancer models, disulfide-containing prodrugs, nanoparticles, nanogels, vaccines, and aptamer-drug conjugates have improved controlled release, tumor-cell uptake, or antitumor response[2][4][5][6]. Compared with non-redox-responsive analogues, disulfide-linked systems showed faster drug release, stronger cellular uptake, or higher tumor-selective cytotoxicity in reported experimental models[4][7][8]. For research design, linker electronics, steric hindrance, substituent position, and biorelevant reducing agents such as glutathione should guide stability and cleavage-rate evaluation[2][9].
References:
- [1]. Deng Z, et al. Disulfide-Based Self-Immolative Linkers and Functional Bioconjugates for Biological Applications. Macromol Rapid Commun. 2020 Jan;41(1):e1900531. [Content Brief]
- [2]. Wang Q, et al. Disulfide based prodrugs for cancer therapy. RSC Adv. 2020 Jun 25;10(41):24397-24409. [Content Brief]
- [3]. Yang X, et al. Making smart drugs smarter: The importance of linker chemistry in targeted drug delivery. Med Res Rev. 2020 Nov;40(6):2682-2713. [Content Brief]
- [4]. Conte C, et al. Enhanced uptake in 2D- and 3D- lung cancer cell models of redox responsive PEGylated nanoparticles with sensitivity to reducing extra- and intracellular environments. J Control Release. 2018 May 10;277:126-141. [Content Brief]
- [5]. Kramer K, et al. Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity. Mol Ther. 2017 Jan 4;25(1):62-70. [Content Brief]
- [6]. Wu Y, et al. Improvement of Drug Release from an Aptamer Drug Conjugate Using Reductive-sensitive Linkers for Tumor-targeted Drug Delivery. AAPS J. 2025 May 20;27(4):95. [Content Brief]
- [7]. Drude N, et al. Impact of Glutathione Modulation on Stability and Pharmacokinetic Profile of Redox-Sensitive Nanogels. Small. 2018 Apr;14(14):e1704093. [Content Brief]
- [8]. Ai X, et al. Star-shape redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol-lysine-di-tocopherol succinate for tumor-triggering intracellular doxorubicin rapid release: head-to-head comparison. Macromol Biosci. 2014 Oct;14(10):1415-28. [Content Brief]
- [9]. Phillips DJ, et al. Redox-sensitive materials for drug delivery: targeting the correct intracellular environment, tuning release rates, and appropriate predictive systems. Antioxid Redox Signal. 2014 Aug 10;21(5):786-803. [Content Brief]
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Disulfide Cleavable Linker Related Products (125)
Related Products (125)
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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).
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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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SPDB-sulfo
0 ImagesCat. No.: HY-129370CAS No.: 1628113-16-5SPDB-sulfo is a glutathione cleavable ADC linker used for the antibody-drug conjugate (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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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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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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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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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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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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4-Succinimidyl-oxycarbonyl-α-(2-pyridyldithio)toluene
0 ImagesCat. No.: HY-133538CAS No.: 160854-54-64-Succinimidyl-oxycarbonyl-α-(2-pyridyldithio)toluene is a non-cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Propargyl-PEG1-SS-PEG1-PFP ester
0 ImagesCat. No.: HY-140110CAS No.: 1817735-30-0Propargyl-PEG1-SS-PEG1-PFP ester is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Propargyl-PEG1-SS-PEG1-PFP 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.
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LC-PEG8-SPDP
0 ImagesCat. No.: HY-126497CAS No.: 1252257-56-9LC-PEG8-SPDP is a cleavable ADC linker used for the antibody-drug conjugates (ADCs).
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DBCO-SS-aldehyde
0 ImagesCat. No.: HY-135977CAS No.: 2749492-45-1DBCO-SS-aldehyde is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-SS-aldehyde 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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DMAC-SPDB-sulfo
0 ImagesCat. No.: HY-131084CAS No.: 663599-07-3DMAC-SPDB-sulfo is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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SPDP-PEG12-acid
0 ImagesCat. No.: HY-141353SPDP-PEG12-acid is a cleavable 12 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Boc-amino-PEG3-SS-acid
0 ImagesCat. No.: HY-136037Boc-amino-PEG3-SS-acid is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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(2-Pyridyldithio)-PEG6 acid
0 ImagesCat. No.: HY-1320862-Pyridyldithio-PEG6 acid is a cleavable 6 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Tetrazine-PEG4-SS-Py
0 ImagesCat. No.: HY-130947Tetrazine-PEG4-SS-Py is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetrazine-PEG4-SS-Py 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.
