An irreversible pan-caspase inhibitor
Boc-D-FMK is a cell-permeable broad-spectrum caspase inhibitor that fully inhibits the pro-apoptotic effect of tumor necrosis factor-α (TNFα) with the half maximal inhibition concentration IC50 value of 39 μM [1].
Boc-D-FMK has been found to reduce the activation of nuclear factor kappa light chain enhancer of activated B cells (NF-kB), suppress the phosphorylation of subunit nuclear factor kappa light polypeptide gene enhancer in B cells inhibitor α (IkBα) and inhibits TNF-induced expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) [2].
Moreover, Boc-D-FMK has also effectively attenuated the hepatocyte apoptosis in bile duct-ligated rats potentially improving the survival rates [3].
参考文献:
[1] Cowburn AS, White JF, Deighton J, Walmsley SR, Chilvers ER. z-VAD-fmk augmentation of TNF alpha-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species. Blood. 2005 Apr 1;105(7):2970-2. Epub 2004 Nov 30.
[2] Wu X, Guo R, Chen P, Wang Q, Cunningham PN. TNF induces caspase-dependent inflammation in renal endothelial cells through a Rho- and myosin light chain kinase-dependent mechanism. Am J Physiol Renal Physiol. 2009 Aug;297(2):F316-26. doi: 10.1152/ajprenal.00089.2009. Epub 2009 May 6.
[3] Sheen-Chen SM, Hung KS, Eng HL. Effect of Boc-D-Fmk on hepatocyte apoptosis after bile duct ligation in rat and survival rate after endotoxin challenge. J Gastroenterol Hepatol. 2008 Aug;23(8 Pt 1):1276-9. doi: 10.1111/j.1440-1746.2008.05368.x. Epub 2008 Mar 27.
| Cell experiment [1]: | |
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Cell lines |
C57BL/6 mice renal endothelial cells |
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Preparation method |
The solubility of this compound in DMSO is >11.65 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
100 μM for 3 h |
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Applications |
Renal EC apoptosis after 4 h of TNF exposure was strongly inhibited by pretreatment with the broad-spectrum caspase inhibitor Boc-D-fmk, as well as caspase-3 inhibitor z-DQMD-fmk. Pretreatment with broad-spectrum caspase inhibitor Boc-D-fmk significantly inhibited TNF-induced ICAM-1 and VCAM-1 mRNA expression. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague–Dawley rats |
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Dosage form |
1.5 mg/kg, i.p. |
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Application |
When compared with sham operation, common bile duct ligation with ZFA-fmk (placebo) significantly increased hepatocyte apoptosis. When compared with the OBZFA group, Boc-D-FMK significantly diminished the increased hepatocyte apoptosis in the OBBOC-D group. There is no difference in hepatocyte apoptosis between OBBOC-D and SHAM groups. After endotoxin challenge, the 48 h survival rates were 100%, 87.5% and 62.5% for the SHAM, OBBOC-D and OBZFA groups, respectively。 |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1] Wu X, Guo R, Chen P, Wang Q, Cunningham PN. TNF induces caspase-dependent inflammation in renal endothelial cells through a Rho- and myosin light chain kinase-dependent mechanism. Am J Physiol Renal Physiol. 2009 Aug;297(2):F316-26. doi: 10.1152/ajprenal.00089.2009. Epub 2009 May 6. [2] Sheen-Chen SM, Hung KS, Eng HL. Effect of Boc-D-Fmk on hepatocyte apoptosis after bile duct ligation in rat and survival rate after endotoxin challenge. J Gastroenterol Hepatol. 2008 Aug;23(8 Pt 1):1276-9. doi: 10.1111/j.1440-1746.2008.05368.x. Epub 2008 Mar 27. |
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