Z-Arg-Lys-AOMK is a cathepsin B inhibitor that can cross the blood-brain barrier. Z-Arg-Lys-AOMK reduces cytosolic cathepsin B activity in homogenates of mouse cerebral cortex and hippocampal tissues, and alleviates motor dysfunction associated with CCI-TBI. Z-Arg-Lys-AOMK can be used in the research of traumatic brain injury [1].
In Vivo, Z-Arg-Lys-AOMK (20 mg/kg; i.p.; once daily) reduces cathepsin B activity in the cytoplasm and homogenates of the cerebral cortex and hippocampus in mice induced by CCI-TBI, and restores motor function to 55% of the baseline level at 1 day post-injury[1].
In Vitro, Z-Arg-Lys-AOMK (1.7-5536 nM; 30 min) potently and selectively inhibits recombinant mouse cathepsin B at neutral pH 7.2 (IC50 = 25 nM) with 100-fold lower potency at acidic pH 4.6, and does not inhibit other mouse cysteine cathepsins (C, H, L, X) at relevant concentrations[1].
References:
[1]. Podvin S, et al. Activation of Cytosolic Cathepsin B Activity in the Brain by Traumatic Brain Injury and Inhibition by the Neutral pH Selective Inhibitor Probe Z-Arg-Lys-AOMK. ACS Chem Neurosci. 2025;16(7):1297-1308.
In Vivo, Z-Arg-Lys-AOMK (20 mg/kg; i.p.; once daily) reduces cathepsin B activity in the cytoplasm and homogenates of the cerebral cortex and hippocampus in mice induced by CCI-TBI, and restores motor function to 55% of the baseline level at 1 day post-injury[1].
In Vitro, Z-Arg-Lys-AOMK (1.7-5536 nM; 30 min) potently and selectively inhibits recombinant mouse cathepsin B at neutral pH 7.2 (IC50 = 25 nM) with 100-fold lower potency at acidic pH 4.6, and does not inhibit other mouse cysteine cathepsins (C, H, L, X) at relevant concentrations[1].
References:
[1]. Podvin S, et al. Activation of Cytosolic Cathepsin B Activity in the Brain by Traumatic Brain Injury and Inhibition by the Neutral pH Selective Inhibitor Probe Z-Arg-Lys-AOMK. ACS Chem Neurosci. 2025;16(7):1297-1308.