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Apoptosis: Caspase Inhibitors
 | | | Table 1: Selected Inhibitors | Inhibitors | Related Products
Activation of caspases is one of the most widely recognized features of apoptosis. Caspases are cysteine-dependent, aspartate-specific proteases. They exist as latent precursors, which, when activated, initiate the death program by destroying key components of the cellular infrastructure and activating factors that mediate damage to the cells. Thus far, 14 members of the caspase family have been identified, 11 of which are present in humans. Caspases have been categorized into upstream initiators and downstream executioners. A distinctive feature of caspases is the absolute requirement of an aspartic acid residue in the substrate P1 position. The P4 residue is important in substrate recognition and specificity. Generally, catalysis involves a cysteine protease mechanism. The tetrapeptide corresponding to the substrate P4 - P1 residues is sufficient to recognize both caspase-1 and caspase-3. This also forms the basis of designing novel inhibitors of caspases.
Caspase activation is generally considered as the “point of no return” in apoptotic pathways. Caspases are activated via two major pathways: the receptor-mediated (Fas ligand or TNFa-mediated) pathway and the mitochondrial pathway. The receptor-mediated pathway leads to the activation of pro-caspase-8. In the mitochondrial pathway pro-apoptotic members of the Bcl-2 family associate with mitochondria and direct the release of cytochrome c (Cyt c) and other proteins, which activate pro-caspase-9.
Caspase inhibitors act by binding to the active site of caspases either in a reversible or irreversible manner. Inhibitor design includes a peptide recognition sequence attached to a functional group such as an aldehyde (CHO), chloromethylketone (CMK), or fluoromethylketone (FMK). The peptide recognition sequence corresponding to that found in endogenous substrates determines the specificity of a particular caspase. For example, compounds with the Ac-YVAD-CHO sequence are potent inhibitor of caspases-1 (Ki ≈ 10 nM), and exhibit very weak inhibitory effect on caspases-3 and -7 (Ki ≥ 50 mM). Exclusion of the tyrosine residue from the inhibitor peptide results in a potent but less specific inhibitor, for example; Z-VAD-FMK inhibits not only caspases-1 and -4, but also caspases-3 and -7. | | | | | | | | | Table 1: Selected Caspase Inhibitors | | | | | | | | Caspase
Inhibitor I | | 467.5 | Z-VAD(OMe)-FMK‡ | √ | - | General | | Caspase Inhibitor I, Biotin Conjugate | | 672.8 | Biotin-X-VAD(OMe)-FMK‡ | | - | General | | Caspase Inhibitor II | | 329.4 | Ac-VAD-CHO† | - | √ | General | | Caspase Inhibitor II, Cell Permeable | | 1827.3 | Ac-AAVALLPAVLLALLAPVAD-CHO | √ | √ | General |
|  | | | | | | Caspase Inhibitors |
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| Caspase Inhibitor I |
627610 |
| InSolution™ Caspase Inhibitor I |
627609 |
| Caspase Inhibitor I, Biotin Conjugate |
218742 |
| Caspase Inhibitor II |
218735 |
| Caspase Inhibitor II, Cell-Permeable |
218830 |
| Caspase Inhibitor III |
218745 |
| Caspase Inhibitor IV |
218784 |
| Caspase Inhibitor VI |
219007 |
| InSolution™ Caspase Inhibitor VI |
219011 |
| Caspase Inhibitor VIII |
218729 |
| Caspase Inhibitor X |
218723 |
| Caspase-2 Inhibitor I |
218744 |
| Caspase-3 Inhibitor II |
264155 |
| Caspase-5 Inhibitor I |
218753 |
| Caspase Inhibitor, Negative Control |
342000 |
| Caspase-1 Inhibitor I |
400010 |
| Caspase-1 Inhibitor I, Cell-Permeable |
400011 |
| Caspase-1 Inhibitor II |
400012 |
| Caspase-1 Inhibitor IV |
400015 |
| Caspase-1 Inhibitor VI |
218746 |
| Caspase-2 Inhibitor II |
218814 |
| Caspase-3 Inhibitor I |
235420 |
| Caspase-3 Inhibitor I, Biotin Conjugate |
235422 |
| Caspase-3 Inhibitor I, Cell-Permeable |
235423 |
| InSolution™ Caspase-3 Inhibitor I, Cell-Permeable |
235427 |
| Caspase-3 Inhibitor II, Biotin Conjugate |
218747 |
| Caspase-3 Inhibitor III |
218750 |
| Caspase-3 Inhibitor IV |
235421 |
| Caspase-3 Inhibitor V |
219002 |
| Caspase-3 Inhibitor VII |
219012 |
| InSolution™ Caspase-3 Inhibitor II |
264156 |
| Caspase-3/7 Inhibitor II |
218832 |
| Caspase-3/7 Inhibitor I |
218826 |
| Caspase-4 Inhibitor I |
218755 |
| Caspase-4 Inhibitor I, Cell-Permeable |
218766 |
| Caspase-6 Inhibitor I |
218757 |
| Caspase-6 Inhibitor II, Cell-Permeable |
218767 |
| Caspase-8 Inhibitor II |
218759 |
| InSolution™ Caspase-8 Inhibitor II |
218840 |
| Caspase-8 Inhibitor I, Cell-Permeable |
218773 |
| Caspase-9 Inhibitor I |
218761 |
| InSolution™ Caspase-9 Inhibitor I |
218841 |
| Caspase-9 Inhibitor II, Cell-Permeable |
218776 |
| Caspase-9 Inhibitor III |
218728 |
| Caspase-1 Inhibitor II, Biotin Conjugate |
400022 |
| Caspase-1 Inhibitor V |
400019 |
| Caspase-13 Inhibitor I |
219005 |
| Caspase-13 Inhibitor II |
219009 |
| CrmA, Recombinant |
PF122 |
| Granzyme B Inhibitor I |
368050 |
| Granzyme B Inhibitor II |
368055 |
| Granzyme B Inhibitor IV |
368056 |
| Group III Caspase Inhibitor I |
368620 |
| Procaspase-3 Activator, PAC-1 |
529661 |
| InSolution™ Q-VD-OPh, Non-O-methylated |
551476 |
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| | | | Other Related Products | Product | Cat. No. | Comments | | Caspase Inhibitor Set I | | The set of 3 separate vials. 1 mg of: - Caspase-3 Inhibitor II, Z-DEVD-FMK (Cat. No. 264155)
- Caspase-1 Inhibitor I, Ac-YVAD-CHO (Cat. No. 400010)
- Caspase Inhibitor I, Z-VAD-FMK (Cat. No. 627610)
| | Caspase Inhibitor Set II | | The set of 8 separate vials. Each set contains 250 mg of: - Caspase-1 Inhibitor VI, Z-YVAD-FMK (Cat. No. 218746)
- Caspase-2 Inhibitor I, Z-VDVAD-FMK (Cat. No. 218744)
- Caspase-3 Inhibitor II, Z-DEVD-FMK (Cat. No. 264155)
- Caspase-5 Inhibitor I, ZWEHD- FMK (Cat. No. 218753)
- Caspase-6 Inhibitor I, Z-VEIDFMK (Cat. No. 218757)
- Caspase-8 Inhibitor II, Z-IETD-FMK (Cat. No. 218759)
- Caspase-9 Inhibitor I, Z-LEHD-FMK (Cat. No. 218761)
- Caspase Inhibitor III, Boc-D-FMK (Cat. No. 218745)
| | Caspase Inhibitor Set III | | A set of 8 separate vials. Each set contains a ready-to-use DMSO solution of irreversible inhibitors of various members of the caspase-family proteases. Contains 25 ml (2 mM) each of: - Caspase-1 Inhibitor VI, Z-YVAD-FMK(Cat. No. 218746)
- Caspase-2 Inhibitor I, Z-VDVAD-FMK (Cat. No. 218744)
- Caspase-3 Inhibitor II, Z-DEVD-FMK (Cat. No. 264155)
- Caspase-5 Inhibitor I, Z-WEHD-FMK (Cat. No. 218753)
- Caspase-6 Inhibitor I, Z-VEID-FMK(Cat. No. 218757)
- Caspase-8 Inhibitor II, Z-IETD-FMK (Cat. No. 218759)
- Caspase-9 Inhibitor I, Z-LEHD-FMK (Cat. No. 218761)
- Caspase Inhibitor I, Z-VAD-FMK (Cat. No. 627610)
| | Caspase Inhibitor Set IV | | A set of 6 separate vials. Each set contains a ready-to-use solution of reagents for caspase inhibition studies and an apoptosis inducer. Contains 25 ml of a 10 mM solution in DMSO of: - Caspase-3 Inhibitor II, Z-DEVD-FMK (Cat. No. 264155)
- Caspase-8 Inhibitor II, Z-IETD-FMK (Cat. No. 218759)
- Caspase-9 Inhibitor I, Z-LEHD-FMK (Cat. No 218761)
- General caspase inhibitor, Z-VAD-FMK (Cat. No. 627610)
- The negative control Z-FA-FMK (Cat. No. 342000)
- An aqueous solution (100 ml, 10.5 mM) of an apoptosis inducer, Doxorubicin, Hydrochloride (Cat. No. 324380).
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