Protease Cleavable Linker
Protease-cleavable linkers connect targeting units to payloads and enable conditional drug release after protease processing in ADCs and related drug conjugates[1]. Mechanistically, Val-Cit and related peptide linkers support lysosomal cathepsin-mediated payload release, while plasma stability remains a central design requirement[1][2]. In tumor models, cleavable Val-Cit or Val-Ala systems released MMAE after intracellular or extracellular proteolysis and produced antitumor activity, whereas noncleavable designs reduced activity in comparable settings[3][4]. Compared with Val-Cit, Val-Ala, glutamic acid-Val-Cit, EGCit, and exo-cleavable designs addressed isoform-like sequence differences in linker susceptibility, including mouse carboxylesterase, neutrophil elastase, aggregation, and premature release[2][5][6][7]. For research applications, these linkers guide ADC, albumin-drug conjugate, and immune-stimulating antibody conjugate design by balancing protease access, tumor payload release, plasma stability, and species-relevant preclinical evaluation[6][8][9].
References:
- [1]. Sutherland MS, et al. Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem. 2006 Apr 14;281(15):10540-7. [Content Brief]
- [2]. Balamkundu S, et al. Lysosomal-Cleavable Peptide Linkers in Antibody-Drug Conjugates. Biomedicines. 2023 Nov 16;11(11):3080. [Content Brief]
- [3]. Dal Corso A, et al. Protease-Cleavable Linkers Modulate the Anticancer Activity of Noninternalizing Antibody-Drug Conjugates. Bioconjug Chem. 2017 Jul 19;28(7):1826-1833. [Content Brief]
- [4]. Gébleux R, et al. Non-internalizing antibody-drug conjugates display potent anti-cancer activity upon proteolytic release of monomethyl auristatin E in the subendothelial extracellular matrix. Int J Cancer. 2017 Apr 1;140(7):1670-1679. [Content Brief]
- [5]. Anami Y, et al. Glutamic acid-valine-citrulline linkers ensure stability and efficacy of antibody-drug conjugates in mice. Nat Commun. 2018 Jun 28;9(1):2512. [Content Brief]
- [6]. Ha SYY, et al. An Enzymatically Cleavable Tripeptide Linker for Maximizing the Therapeutic Index of Antibody-Drug Conjugates. Mol Cancer Ther. 2022 Sep 6;21(9):1449-1461. [Content Brief]
- [7]. Watanabe T, et al. Exo-Cleavable Linkers: Enhanced Stability and Therapeutic Efficacy in Antibody-Drug Conjugates. J Med Chem. 2024 Oct 24;67(20):18124-18138. [Content Brief]
- [8]. Bernardim B, et al. Cathepsin B Processing Is Required for the In Vivo Efficacy of Albumin-Drug Conjugates. Bioconjug Chem. 2024 Feb 21;35(2):132-139. [Content Brief]
- [9]. Bisbal Lopez L, et al. Ex vivo mass spectrometry-based biodistribution analysis of an antibody-Resiquimod conjugate bearing a protease-cleavable and acid-labile linker. Front Pharmacol. 2023 Dec 6;14:1320524. [Content Brief]
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Protease Cleavable Linker Related Products (83)
Related Products (83)
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DBCO-PEG4-acetic-Val-Cit-PAB
0 ImagesCat. No.: HY-136098Purity: 99.23%DBCO-PEG4-acetic-Val-Cit-PAB is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG4-acetic-Val-Cit-PAB 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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DBCO-PEG3 acetic-EVCit-PAB
0 ImagesCat. No.: HY-136096CAS No.: 2253947-17-8DBCO-PEG3 acetic-EVCit-PAB is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG3 acetic-EVCit-PAB 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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Mal-PEG4-VC-PAB-DMEA
0 ImagesCat. No.: HY-126668CAS No.: 1569261-93-3Mal-PEG4-VC-PAB-DMEA is a cleavable ADC linker containing a Maleimide group. Mal-PEG4-VC-PAB-DMEA is used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG4-VCP-NB
0 ImagesCat. No.: HY-160981CAS No.: 1345681-54-0Mal-PEG4-VCP-NB (Compound 17) is a degradable ADC linker containing a maleimide group, 4 PEG units and VCP NB.
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PDP-C1-Ph-Val-Cit
0 ImagesCat. No.: HY-126533CAS No.: 1610769-13-5PDP-C1-Ph-Val-Cit is a cleavable ADC linker used for antibody-drug conjugates (ADCs).
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OPSS-Val-Cit-PAB-OH
0 ImagesCat. No.: HY-141144CAS No.: 3047198-15-9OPSS-Val-Cit-PAB-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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mDPR(Boc)-Val-Cit-PAB
0 ImagesCat. No.: HY-126670CAS No.: 2281797-55-3mDPR(Boc)-Val-Cit-PAB is a cleavable ADC linker used as a linker for antibody-drug conjugates (ADC).
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Fmoc-Phe-Lys(Boc)-PAB
0 ImagesCat. No.: HY-139353CAS No.: 206133-42-8Fmoc-Phe-Lys(Boc)-PAB is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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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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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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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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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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Mal-PEG3-VCP-NB
0 ImagesCat. No.: HY-160982CAS No.: 1345681-77-7Mal-PEG3-VCP-NB (Compund 25c) is a degradable ADC linker containing a maleimide group, 3-unit PEG and VCP NB.
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DBCO-PEG3-propionic EVCit-PAB
0 ImagesCat. No.: HY-136141DBCO-PEG3-propionic EVCit-PAB is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG3-propionic EVCit-PAB 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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MC-Val-Cit-PAB-NH-C2-NH-Boc
0 ImagesCat. No.: HY-132973CAS No.: 1616727-22-0MC-Val-Cit-PAB-NH-C2-NH-Boc is a cathepsin cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Mal-PEG4-VA
0 ImagesCat. No.: HY-126669CAS No.: 1800456-31-8Mal-PEG4-VA is a cleavable ADC linker containing a Maleimide group. Mal-PEG4-VA is used for making antibody-drug conjugate.
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Phe-Lys(Trt)-PAB
0 ImagesCat. No.: HY-129349CAS No.: 1116085-99-4Phe-Lys(Trt)-PAB is a cathepsin B substrate, and a cleavable ADC linker. Phe-Lys(Trt)-PAB acts as a lysosomally cleavable substrate for cysteine protease cathepsin B, with cleavage enabling linked anticancer drug release via self-immolative spacer . Phe-Lys(Trt)-PAB can be used for synthesis of ADCs.
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DBCO-PEG4-Propionic-Val-Cit-PAB
0 ImagesCat. No.: HY-136103DBCO-PEG4-Propionic-Val-Cit-PAB is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-PEG4-Propionic-Val-Cit-PAB 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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SC-Val-Cit-PAB
0 ImagesCat. No.: HY-126667CAS No.: 2922649-64-5SC-Val-Cit-PAB is a cleavable ADC linker for antibody-drug conjugates (ADCs).
