An isatin sulfonamide-based inhibitor of caspase-3 and caspase-7
Caspase-3/7 inbibitor I is a potent, reversible, isatin sulfonamide-based inhibitor of caspase-3 (KI(app) = 60 nM) and caspase-7 (KI(app) = 170 nM). Is a weaker inhibitor of caspase-9 (Ki(app) = 3.1 mM). It Has only a trivial effect (Ki(app) >25 mM) on the activities of caspase-1, caspase-2, caspase-4, caspase-6, and caspase-8. It has been shown to inhibit apoptosis in camptothecin treated Jurkat cells (IC50 ~50 μM). Also it has been reported to inhibit apoptosis in chondrocytes (44% inhibition at 10 μM and 98% inhibition at 50 μM). Selectivity for caspases-3 and 7 involves unique hydrophobic residues in the S2 pocket surrounding the catalytic cysteine residue. [1] [2] In some systems inhibition of caspases-3 and -7 can prevent apoptosis and may therefore have important therapeutic implications. [3]
A potent, cell-permeable, and specific, reversible inhibitor of caspase-3 (Ki = 60 nM) and caspase-7 (Ki = 170 nM).
参考文献:
1. Lee, D., et al. 2001. J. Med. Chem. 44, 2015.
2. Lee, D., et al. 2000. J. Biol. Chem. 275, 16007.
3. Clements, K. M., Burton‐Wurster, N., Nuttall, M. E., & Lust, G. (2005). Caspase‐3/7 inhibition alters cell morphology in mitomycin‐c treated chondrocytes. Journal of cellular physiology, 205(1), 133-140.
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Cell lines |
Human Jurkat T cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
50 μM |
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Applications |
Cells were treated with camptothecin to induce cell death, and the ability of the compound to inhibit cell death was assessed by FACS analysis. A good correlation exists between relative cell-based activities of the compound with its in vitro isolated caspase 3 or 7 inhibition activites. The compound exhibited 54% inhibition of apoptosis at 50 μM and 22% at 10 μM. |
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Animal models |
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Dosage form |
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Applications |
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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] Lee D, Long S A, Murray J H, et al. Potent and selective nonpeptide inhibitors of caspases 3 and 7. Journal of medicinal chemistry, 2001, 44(12): 2015-2026. |
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