Z-IETD-FMK

Z-IETD-FMK (Z-IE(OMe)TD(OMe)-FMK) is a selective and cell permeable caspase-8 inhibitor. Z-IETD-FMK is also a granzyme B inhibitor.

Product information

CAS Number: 210344-98-2

Molecular Weight: 654.68

Formula: C30H43FN4O11

Synonym:

Z-IE(OMe)TD(OMe)-FMK

Chemical Name: methyl (3S)-3-[(2S, 3R)-2-[(2S)-2-[(2S, 3S)-2-{[(benzyloxy)carbonyl]amino}-3-methylpentanamido]-5-methoxy-5-oxopentanamido]-3-hydroxybutanamido]-5-fluoro-4-oxopentanoate

Smiles: CC[C@H](C)[C@H](NC(=O)OCC1C=CC=CC=1)C(=O)N[C@@H](CCC(=O)OC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)OC)C(=O)CF

InChiKey: PHLCQASLWHYEMX-DEKIMQJDSA-N

InChi: InChI=1S/C30H43FN4O11/c1-6-17(2)25(35-30(43)46-16-19-10-8-7-9-11-19)28(41)32-20(12-13-23(38)44-4)27(40)34-26(18(3)36)29(42)33-21(22(37)15-31)14-24(39)45-5/h7-11,17-18,20-21,25-26,36H,6,12-16H2,1-5H3,(H,32,41)(H,33,42)(H,34,40)(H,35,43)/t17-,18+,20-,21-,25-,26-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 41.67 mg/mL (63.65 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Z-IETD-FMK causes full inhibition only of the proapoptotic effect of TNFα with an IC50 of 0.46 μM. Z-IETD-FMK and Z-VAD-FMK at non-toxic doses are found to be immunosuppressive and inhibit human T cell proliferation induced by mitogens and IL-2. They are shown to block NF-κB in activated primary T cells, but have little inhibitory effect on the secretion of IL-2 and IFN-γ during T cell activation. Z-IETD-FMK inhibits the cleavage of caspase-8 and only partially inhibits the cleavage of caspase-3 and PARP. Z-IETD-FMK can prevent the execution of apoptosis in retinal cells exposed to different apoptotic stimuli.

In Vivo:

Pharmacological inhibition of caspase-8 by z-IETD-FMK robustly reduces tumour outgrowth and this is closely associated with a reduction in the release of pro-inflammatory cytokines, IL-6, TNF-α, IL-18, IL-1α, IL-33, but not IL-1β. Furthermore, inhibition of caspase-8 reduces the recruitment of innate suppressive cells, such as myeloid-derived suppressor cells, but not of regulatory T cells to lungs of tumour-bearing mice.

References:

1. Cowburn AS, et al. z-VAD-fmk augmentation of TNF alpha-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species.
2. Lawrence CP, et al. 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.
3. Tezel G, et al. Inhibition of caspase activity in retinal cell apoptosis induced by various stimuli in vitro. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2660-7.

Products are for research use only. Not for human use.