| Description | CA 074 is a potent inhibitor of cathepsin B with a Ki value of 2 to 5 nM.CA 074 inhibits ischemic hippocampal neuronal death in primates and attenuates retinopathy and optic neuritis in experimental autoimmune encephalomyelitis induced by SJL/J mice. |
| In vitro | CA-074, a synthetic analogue of E-64 developed through rational drug design, is an irreversible inhibitor of most lysosomal cysteine proteinases. It exploits the dipeptidylcarboxypeptidase activity of cathepsin B. With a Ki of 2 to 5 nM, CA-074 selectively inhibits cathepsin B within living cells, provided that experimental conditions allow significant fluid-phase endocytosis of the drug[2]. Notably, CA-074 demonstrates significantly greater inhibitory effects on purified rat cathepsin B (10000-30000 times) compared to cathepsin H and L, for which the initial Kis are about 40-200 μM[3]. |
| In vivo | The intraperitoneal injection of compound CA-074 into rats effectively and selectively inhibits cathepsin B activity[1]. Following intravenous administration of CA-074 immediately after the ischemic insult, it preserves 67% of CA1 neurons from delayed neuronal death on day 5 in eight monkeys undergoing 20 minutes of brain ischemia. The extent of inhibition is excellent in three of eight monkeys and good in five of eight monkeys[1]. |
| Target activity | Cathepsin B:2-5 nM(Ki) |
| molecular weight | 383.44 |
| Molecular formula | C18H29N3O6 |
| CAS | 134448-10-5 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 100 mg/mL (260.80 mM), Sonication is recommended. |
| References | 1. Yamashima T, 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. 1998 May;10(5):1723-33. 2. Montaser M, et al. CA-074, but not its methyl ester CA-074Me, is a selective inhibitor of cathepsin B within living cells. Biol Chem. 2002 Jul-Aug;383(7-8):1305-8. 3. Towatari T, et al. Novel epoxysuccinyl peptides. A selective inhibitor of cathepsin B, in vivo. FEBS Lett. 1991 Mar 25;280(2):311-5. |