KLK5
Kallikrein-related peptidase 5 (KLK5) is a serine protease predominantly expressed in the epidermis, where it regulates desquamation and maintains skin barrier homeostasis[1][2]. Mechanistically, KLK5 initiates a proteolytic cascade by activating downstream kallikreins such as KLK7, which amplifies epidermal proteolytic activity[1]. Dysregulated KLK5 activity contributes to skin pathologies, including Netherton syndrome and rosacea, by promoting overproduction of antimicrobial peptide LL-37 and inducing inflammatory signaling via TLR4/NF-κB pathways[2]. In experimental models, genetic ablation of KLK5 in Spink5-deficient mice attenuates disease phenotypes, confirming KLK5 as a critical driver of proteolytic and inflammatory processes in vivo[1]. Compared with related isoforms such as KLK7 and KLK8, KLK5 exhibits a unique substrate specificity and tissue localization, distinguishing its functional contributions to epidermal homeostasis and disease[1][3]. Small molecule inhibitors and natural compounds like lithospermic acid have demonstrated selective KLK5 inhibition, reducing pro-inflammatory cytokines and restoring metabolic balance in experimental rosacea models[2]. These pharmacological tools enable precise modulation of KLK5 activity, supporting its utility in preclinical studies and potential therapeutic development[2][1]. Overall, KLK5 serves as a central regulatory node in skin proteolytic cascades, offering mechanistic insight and intervention points for inflammatory dermatological conditions.
References:
- [1]. Sotiropoulou G, et al. Novel specific activity-based probes validate KLK proteases as druggable targets. Cancer Biol Ther. 2022 Dec 31;23(1):401-403. [Content Brief]
- [2]. Xu J, et al. Lithospermic acid, a novel KLK5 inhibitor, ameliorates rosacea by suppressing the TLR4/NF-κB signaling pathway and rectifying phenylalanine metabolism. Front Immunol. 2026 Jan 26;17:1734997. [Content Brief]
- [3]. Koumandou VL, et al. Evolution of the plasma and tissue kallikreins, and their alternative splicing isoforms. PLoS One. 2013 Jul 10;8(7):e68074. [Content Brief]
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KLK5 Related Products (4)
Related Products (4)
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Kallikrein 5-IN-2 TFA
0 ImagesCat. No.: HY-148949APurity: 99.53%Kallikrein 5-IN-2 TFA is the TFA salt form of Kallikrein 5-IN-2 (HY-148949). Kallikrein 5-IN-2 TFA is a selective inhibitor for kallikrein 5 (KLK5) with pIC50 of 7.1. Kallikrein 5-IN-2 TFA is non-phototoxic (100 μg/mL) and non-irritant. Kallikrein 5-IN-2 is stable at pH 4-pH 8 under non-oxidative condition. Kallikrein 5-IN-2 is potent in ameliorating the Netherton syndrome.
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DKFZ-251
0 ImagesCat. No.: HY-124714CAS No.: 2222059-70-1DKFZ-251 is a kininogenase-related peptidase KLK6 inhibitor (IC50=0.47 μM), and also exhibits certain inhibitory activity against KLK5 and KLK7 (IC50 values are 1.1 nM and 73 nM, respectively). DKFZ-251 transiently acylates the catalytic serine of KLK6 to form a long-lived acyl-enzyme complex that inhibits enzyme function. DKFZ-251 is a phenotypic modulator that alters cell proliferation capacity and regulates epithelial-mesenchymal transition (EMT). DKFZ-251 can be used in research related to head and neck cancer.
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KLK5-IN-1
0 ImagesCat. No.: HY-P11840KLK5-IN-1 is a selective kallikrein 5 (KLK5) inhibitor with an IC50 of 14 nM and a Ki of 11 nM. KLK5-IN-1 reduces KLK5-mediated PAR2-dependent calcium mobilization. KLK5-IN-1 improves epithelial barrier integrity. KLK5-IN-1 can be used in research related to atopic dermatitis and Netherton syndrome.
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GSK951
0 ImagesCat. No.: HY-150085CAS No.: 2393881-77-9GSK951 is a highly potent, selective, and reversibly covalent KLK5 inhibitor, with an IC50 of approximately 250 pM and a pIC50 of 9.6 against hKLK5. It exhibits over 100-fold selectivity over KLK7, KLK14, matriptase, and elastase. GSK951 binds to the catalytic site of KLK5 via covalent interaction with the catalytic serine, with a slow dissociation rate. GSK951 improves skin barrier function, reduces transepidermal water loss, decreases the expression of proinflammatory cytokines, and inhibits the elevated KLK5 protease activity in the stratum corneum. GSK951 can be used in studies related to skin barrier dysfunction.
