Table 7.
Protease inhibition profiles of small molecule inhibitors of cathepsin B, from studies of TBI and TBI-related animals.
| Name of inhibitor | Inhibition profile | Notes | Reference |
|---|---|---|---|
| E64 (L-trans-epoxysuccinyl-leucylamido(4-guanidino)butane | Cathepsins B, L, H, K, S, F, O, V, W, X, calpains 1 and 2, and papain | Irreversible inhibitor | (70, 257–260) |
| E64d (EST, Loxistatin, ethyl (2S,3S)-3-[[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylate) | Cathepsins B, L, H, K, S, F, O, V, W, X, calpains 1 and 2, and papain | Clinical use Irreversible inhibitor |
(261, 262) |
| E64c (Loxistatin acid, EP-475, (2S,3S)-3-[[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylic acid) | Cathepsins B, L, H, K, S, F, O, V, W, X, calpains 1 and 2, and papain | Clinical use Irreversible inhibitor |
(261, 263) |
| CA-074 (N-(L-3-trans-Propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-proline) | Cathepsin B (absolute specificity) | Irreversible inhibitor | (264–266) |
| CA-074Me (N-(L-3-trans-Propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline methyl ester) | Cathepsins B and L | Irreversible inhibitor | (267–269) |
| LHVS (morpholinurea-leucine-homophenylalanine-vinylsulfone-phenyl) | Cathepsins S, B, and L | Irreversible inhibitor | (146) |
| Z-FA-FMK (methyl (3S)-5-fluoro-3-[[(2S)-2-[[(2S)-3-methyl-2(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxopentanoate) | Cathepsins B, L, and S; caspases 2, 3, 6, and 7; cruzain; and papain | Irreversible inhibitor | (112) |
| Z-DEVD-FMK (methyl (4S)-5-[[(2S)-1-[[(3S)-5-fluoro-1-methoxy-1,4-dioxopentan-3-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-[[(2S)-4-methoxy-4-oxo-2-(phenylmethoxycarbonylamino)butanoyl]amino]-5-oxopentanoate) | Cathepsins B and L, and caspases 3, 6, 7, 8, and 10 | Irreversible inhibitor | (247, 270–272) |
| CP-1 (O-benzyl, OBzl, carbobenoxy, Cbz-Phe-Ser(OBzl)-CHN2, 2[methyl-(4-phenylbenzoyl)amino]benzoic acid) | Cathepsins B and L | Reversible inhibitor | (110, 251, 253) |
| K11777 (N-methyl-Piperazine-Phe-homoPhe-vinylsufone-phenyl) | Cathepsins B and L, and cruzain | Irreversible inhibitor | (43, 273) |
| NC-2300 (VEL-0230, sodium (2S,3S)-3-(((S)-1-isobutoxy-4-methylpentan-2-yl)carbamoyl)oxirane-2-carboxylate) | Cathepsins K, B, and S | Irreversible inhibitor | (104) |
Short names of inhibitors are shown in bold. Parentheses indicate other names used for the inhibitor, including chemical names.