Calpeptin is a reversible and cell-permeable cysteine cathepsin inhibitor. The ID50 values of Calpeptin for calpain I and II (porcine), papain, and platelet calpain I are 52nM, 34nM, 138nM, and 20nM, respectively[1]. Calpeptin alleviates apoptosis and secondary inflammatory changes in muscle cells[2].
In vitro, Calpeptin (1 and 5μM; 24h) attenuates apoptosis and secondary inflammatory changes induced by extracellular inflammatory stimulation in the muscle cells[2]. Calpeptin (0, 25, 50 and 100μmol/L; 4 days) inhibited PSC activation and proliferation and promoted PSC apoptosis[3].
In vivo, Calpeptin (1.75mg/kg/day; 1 week; i.p.) effectively reduced the expression of Calpain‐2 and TXNIP/NLRP3 inflammasome-related proteins, improved the decreased pericyte marker (PDGFR‐β) and cognitive impairment in hippocampus of DM rats[4]. Calpeptin (2mg/kg/100μl; 2 or 8 days; i.p.) administration after birth affects synaptic development in neonatal rats by inhibiting the Akt/mTOR signaling pathway, thereby perturbing hippocampal function[5]. Calpeptin (200μg/kg; 4 week; i.p.) is neuroprotective against acrylamide-induced neuropathy in rats[6].
References:
[1] Tsujinaka T, Kajiwara Y, Kambayashi J, et al. Synthesis of a new cell penetrating calpain inhibitor (calpeptin). Biochem Biophys Res Commun. 1988 Jun 30;153(3):1201-8.
[2] Shen J, Xiao W, Zong G, et al. Calpain Inhibitor Calpeptin Improves Pancreatic Fibrosis in Mice with Chronic Pancreatitis by Inhibiting the Activation of Pancreatic Stellate Cells. Curr Mol Pharmacol. 2024;17:e18761429241425.
[3] Nozaki K, Das A, Ray SK, et al. Calpeptin attenuated apoptosis and intracellular inflammatory changes in muscle cells. J Neurosci Res. 2011 Apr;89(4):536-43.
[4] Qiao L, Yi S, Li T, et al. Calpeptin improves the cognitive function in Alzheimer's disease-like complications of diabetes mellitus rats by regulating TXNIP/NLRP3 inflammasome. J Diabetes Investig. 2024 Oct;15(10):1365-1376.
[5] Song ZJ, Yang SJ, Han L, et al. Postnatal calpeptin treatment causes hippocampal neurodevelopmental defects in neonatal rats. Neural Regen Res. 2019 May;14(5):834-840.
[6] Su B, Guan Q, Wang M, et al. Calpeptin is neuroprotective against acrylamide-induced neuropathy in rats. Toxicology. 2018 May 1;400-401:1-8.
Calpeptin是一种可逆且可穿透细胞的半胱氨酸组织蛋白酶抑制剂。Calpeptin对钙蛋白酶I和II（猪源）、木瓜蛋白酶以及血小板钙蛋白酶I的ID50值分别为52nM, 34nM, 138nM和20nM[1]。Calpeptin可减轻肌肉细胞中的凋亡和继发性炎症变化[2]。
在体外实验中，Calpeptin（1和5μM; 24小时）可减轻肌肉细胞由细胞外炎症刺激诱导的凋亡和继发性炎症变化[2]。Calpeptin（0, 25, 50和100μmol/L; 4天）抑制了胰星状细胞（PSC）的激活和增殖，并促进PSC凋亡[3]。
在体内实验中，Calpeptin（1.75mg/kg/天; 1周; 腹腔注射）有效降低了糖尿病大鼠海马中Calpain-2和TXNIP/NLRP3炎症体相关蛋白的表达，改善了降低的周细胞标记物（PDGFR-β）和认知障碍[4]。出生后给予Calpeptin（2mg/kg/100μl; 2天或8天; 腹腔注射）可通过抑制Akt/mTOR信号通路影响新生大鼠的突触发育，从而扰乱海马体功能[5]。Calpeptin（200μg/kg; 4周; 腹腔注射）对丙烯酰胺诱导的大鼠神经病变具有神经保护作用[6]。