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In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Z-IETD-FMK is an inhibitor of caspase 8 [1].
Z-IETD-FMK inhibits T cell proliferation induced by PHA or anti-CD3 plus anti-CD28 without toxicity of resting T cells. The mechanism of this inhibition of Z-IETD-FMK has been proved not through the effect on IL-2 secretion or IFN-γ production but the decrease of CD25 expression. Experiments show that Z-IETD-FMK has no effect on normal cell growth when there is no activation signal. Z-IETD-FMK has also been found to significantly inhibit NF-κB activation when the concentration is 100μM [1].
Apart from the ability of inhibiting cell proliferation, Z-IETD-FMK is reported to inhibit TRAIL-mediated killing in cells. It protects the procaspases 9, 2, and 3, and protects PARP to a similar extent in both HCT116 and SW480 cells [2].
References:[1] C.P. Lawrence, S.C. Chow. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties. Toxicology and Applied Pharmacology. 2012, 265: 103-112. [2] Nesrin Özören, Kunhong Kim, Timothy F. Burns, et al. The caspase 9 inhibitor Z-LEHD-FMK protects human liver cells while permitting death of cancer cells exposed to tumor necrosis factor-related apoptosis-inducing ligand. Cancer Research. 2000, 60: 6259-6265.
Cell lines
Purified CD4+ and CD8+ T cells.
Preparation method
Limited solubility. 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.
Reaction Conditions
24 h
Applications
T cell proliferation was assayed using [3H]-thymidine incorporation. z-IETD-FMK (100 μM) inhibits T cell proliferation. About 9% of control activated T cells took up PI after activation and in the presence of 100 μM of z-IETD-FMK cell death increases to 23%. In addition, 100 μM z-IETD-FMK decreases the nuclear translocation of p65 in activated T cells.
Animal models
SHIP1-/- (CD45.1) mice
Dosage form
5 mg/kg three times each week for 3 weeks
There is a significant diminution of anatomical pathology in both the small intestine and lungs of Z-IETD-FMK-treated mice compared with vehicle-administered controls. There is also a prominent recovery of viable CD3+ T-cell numbers in small intestine and lung of the Z-IETD-FMK-treated SHIP1-/- hosts, whereas the vehicle-treated SHIP1-/- hosts exhibit the T-cell paucity.
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.
References:
1. Lawrence CP, Chow SC. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties. Toxicol Appl Pharmacol. 2012 Nov 15;265(1):103-12.
2. Park MY, Srivastava N, Sudan R et al. Impaired T-cell survival promotes mucosal inflammatory disease in SHIP1-deficient mice. Mucosal Immunol. 2014 Nov;7(6):1429-39.