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]
-
Protease Cleavable Linker Related Products (83)
Related Products (83)
-
Mal-PEG4-Val-Cit-PAB-OH
0 ImagesCat. No.: HY-140143CAS No.: 2055041-39-7Mal-PEG4-Val-Cit-PAB-OH is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Fmoc-D-Val-Cit-PAB
0 ImagesCat. No.: HY-19318BCAS No.: 1350456-65-3Fmoc-D-Val-Cit-PAB is a cleavable linker for antibody-agent-conjugation (ADC).
-
Fmoc-D-Val-D-Cit-PAB
0 ImagesFmoc-D-Val-D-Cit-PAB is a cleavable linker for antibody-agent-conjugation (ADC).
-
Fmoc-Phe-Lys(Trt)-PAB
0 ImagesCat. No.: HY-136107CAS No.: 1116085-98-3Fmoc-Phe-Lys(Trt)-PAB is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
DBCO-Val-Cit-PABC-OH
0 ImagesCat. No.: HY-130936DBCO-Val-Cit-PABC-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-Val-Cit-PABC-OH is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
-
TCO-PEG1-Val-Cit-OH
0 ImagesCat. No.: HY-130934TCO-PEG1-Val-Cit-OH is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). TCO-PEG1-Val-Cit-OH 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.
-
Mal-Phe-C4-Val-Cit-PAB
0 ImagesCat. No.: HY-126671CAS No.: 3054740-77-8Mal-Phe-C4-Val-Cit-PAB is a cleavable ADC linker containing a Maleimide group. Mal-Phe-C4-Val-Cit-PAB is used for making antibody-drug conjugate.
-
Azide-PEG1-Val-Cit-PABC-OH
0 ImagesCat. No.: HY-136137CAS No.: 2055041-40-0Azide-PEG1-Val-Cit-PABC-OH is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azide-PEG1-Val-Cit-PABC-OH 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.
-
Azido-PEG3-Val-Cit-PAB-OH
0 ImagesCat. No.: HY-140148CAS No.: 2055024-65-0Azido-PEG3-Val-Cit-PAB-OH is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG3-Val-Cit-PAB-OH 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.
-
TCO-PEG1-Val-Cit-PABC-PNP
0 ImagesCat. No.: HY-136100TCO-PEG1-Val-Cit-PABC-PNP is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). TCO-PEG1-Val-Cit-PABC-PNP is a click chemistry reagent, which contains a TCO group that can undergo an inverse electron demand Diels-Alder reaction (iEDDA) with molecules containing Tetrazine groups.
-
Fmoc-Gly3-Val-Cit-PAB-PNP
0 ImagesCat. No.: HY-136108CAS No.: 2647914-16-5Fmoc-Gly3-Val-Cit-PAB-PNP is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
MC(C5)-Val-Cit
0 ImagesCat. No.: HY-141143CAS No.: 2504147-59-3MC(C5)-Val-Cit is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Azido-PEG1-Val-Cit-OH
0 ImagesCat. No.: HY-136034Azido-PEG1-Val-Cit-OH is a cleavable 1 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG1-Val-Cit-OH 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.
-
Aloc-D-Ala-Phe-Lys(Aloc)-PAB-PNP
0 ImagesCat. No.: HY-129351CAS No.: 253863-34-2Aloc-D-Ala-Phe-Lys(Aloc)-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
DBCO-Val-Cit-OH
0 ImagesCat. No.: HY-130935DBCO-Val-Cit-OH is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-Val-Cit-OH is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
-
OPSS-Val-Cit-PAB-PNP
0 ImagesCat. No.: HY-141145CAS No.: 3047198-18-2OPSS-Val-Cit-PAB-PNP is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
Mal-amido-PEG2-Val-Cit-PAB-OH
0 ImagesCat. No.: HY-140146CAS No.: 2504147-53-7Mal-amido-PEG2-Val-Cit-PAB-OH is a cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
-
PAB-Val-Lys-Boc
0 ImagesCat. No.: HY-138651CAS No.: 1432969-86-2PAB-Val-Lys-Boc is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs) for stimulating an immune response.
-
vc-PAB-DMEA-PNU159682
0 ImagesCat. No.: HY-147093CAS No.: 2227350-96-9vc-PAB-DMEA-PNU159682 (compound I.47) can be used to synthesize the ADC molecule based on Sulfomaleimide-based Linker. vc-PAB-DMEA-PNU159682 has good serum stability.
