CA-074

CA-074 is a selective epoxysuccinyl peptide inhibitor of the cysteine protease cathepsin B (K_is = 0.0087, 75, and 233 μM for rat cathepsin B, H, and L, respectively).¹ It inhibits degradation of DQ-collagen IV and DQ-collagen I in 4T1.2 breast cancer cells in a concentration-dependent manner and reduces the number of lung and bone metastases in a 4T1.2 murine mammary cancer model, without affecting primary tumor growth, when administered at a dose of 50 mg/kg.² CA-074 (0.1 and 0.2 mg/animal per day) reduces mercury-induced increases in expression of TNF-α, IL-1β, and the inflammasome component NRLP3 and decreases the severity of mercury-induced skin induration in mice.³ CA-074 also reduces ischemia-induced hippocampal neuron cell death in monkeys.⁴

WARNING This product is not for human or veterinary use.

1. Murata, M., Miyashita, S., Tokoo, C., et al. Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, invitro. FEBS Lett. 280(2), 307-310 (1991).

2. Withana, N.P., Blum, G., Sameni, M., et al. Cathepsin B inhibition limits bone metastasis in breast cancer. Cancer Res. 72(5), 1199-1209 (2012).

3. Toomey, C.B., Cauvi, D.M., Hamel, J.C., et al. Cathepsin B regulates the appearance and severity of mercury-induced inflammation and autoimmunity. Toxicol. Sci. 142(2), 339-349 (2014).

4. Yamashima, T., Kohda, T., Tsuchiya, K., et al. Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: A novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'. Eur. J. Neurosci. 10(5), 1723-1733 (1998).

Varalda, M., Antona, A., Bettio, V., et al. Psychotropic drugs show anticancer activity by disrupting mitochondrial and lysosomal function. Front. Oncol. 10, 562196 (2020).