KLK8

Kallikrein-related peptidase 8 (KLK8) is a secreted serine protease that modulates tissue remodeling and cellular signaling in multiple organs^[1]^[2]. KLK8 regulates cardiomyocyte hypertrophy through epidermal growth factor (EGF) signaling and protease-activated receptor (PAR) pathways, independent of kinin receptor activation^[1]. In vascular endothelium, KLK8 promotes endothelial-to-mesenchymal transition (EndMT) by cleaving VE-cadherin, facilitating plakoglobin nuclear translocation, and enhancing TGF-β1/Smad signaling, thereby contributing to diabetic cardiac fibrosis^[2]. Compared with other KLK family members, KLK8 exhibits tissue-specific expression in myocardium and brain and uniquely interacts with transcriptional regulators including p53 and HIF-1α^[2]^[3]. In neurodegenerative disease models, KLK8 inhibition ameliorates Alzheimer's disease pathology by modulating amyloid-beta precursor processing and tau hyperphosphorylation^[3]. KLK8 expression is responsive to muscarinic acetylcholine receptor (mAChR) agonists, linking its activity to dendritic growth and memory-related neuronal functions^[4]. Selective pharmacological modulation of KLK family members has been achieved using activity-based probes and peptide inhibitors, establishing proof-of-concept for therapeutic targeting of KLKs in cardiovascular, neurodegenerative, and dermatological contexts^[5]^[6]. These inhibitors demonstrate isoform-specificity, enabling distinction of KLK8 function from related KLKs in complex proteolytic cascades^[5]^[6].

References:

[1]. Cao B, et al. Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy. Sci Rep. 2016 Jan 29;7:20024. [Content Brief]

[2]. Du JK, et al. A novel role of kallikrein-related peptidase 8 in the pathogenesis of diabetic cardiac fibrosis. Theranostics. 2021 Feb 20;11(9):4207-4231. [Content Brief]

[3]. Lahiri DK, et al. A cardinal sin when researching neuropsin/KLK8: Thou shalt validate antibodies. Alzheimers Dement. 2017 Sep;13(9):1068-1069. [Content Brief]

[4]. Konar A, et al. M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration and memory recovery by i-Extract from Withania somnifera. Sci Rep. 2019 Sep 30;9(1):13990. [Content Brief]

[5]. 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]

[6]. Chen W, et al. Tissue Kallikrein Inhibitors Based on the Sunflower Trypsin Inhibitor Scaffold - A Potential Therapeutic Intervention for Skin Diseases. PLoS One. 2016 Nov 8;11(11):e0166268. [Content Brief]

KLK8 Inhibitor (1)

KLK8 Related Products (1):

Cat. No.	Product Name	Effect	Purity

HY-148949A

Kallikrein 5-IN-2 TFA	Inhibitor	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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