Z-FA-FMK is an irreversible inhibitor of cathepsin B, including cathepsins B and L, and also inhibits DEVDase caspase activity. Preincubation with Z-FA-FMK could dose-dependently inhibit activation of caspase at concentration of 30, 60 and 150μM in HeLa cell extracts. The activity inhibition of caspase 2, 3, 6, 7 and 9 could be observed. Pre-treatment with 100μM Z-FA-fmk for 1h could inhibit the induction of DEVDase activity by stimuli in intact Jurkat cells, but without cytochrome c release. Pre-treatment with Z-FA-fmk at concentration ranging in 10-100μM for 2h dose-dependently inhibited processing and activation of caspase-2, 3, 7 and 9, as well as cleavage of Bid, induced by treatment with 1μM MX2870-1 for 3h. Z-FA-FMK could partially inhibit the activity of mature effector caspases in intact cells at low concentration and prevent the cleavage and activation of effector caspases initiated by caspase 9 correlating with partial inhibition of mature caspase 9 at higher concentrations[1]. Z-FA-FMK is immunosuppressive in vitro and in vivo. Z-FA-FMK inhibited IL-2-driven T cell proliferation by preventing cells from entering and leaving the cell cycle, and inhibited the IL-2 autocrine system in T lymphocytes at concentration of 100μM. The inhibition of translocation of cellular p65 to the nucleus by z-FA-FMK could be observed in purified T cells costimulated with anti-CD3 and anti-CD28. Z-FA-FMK inhibited the processing of caspase-8 and caspase-3 to their respective subunits in resting T cells stimulated through the Ag receptor but not during Fas-induced apoptosis in proliferating T cells. Administration of 25mg/kg, i.v., increased pneumococcal load in the blood and lungs of MFI mice[2].
Z-FA-FMK significantly increased SMN protein levels in SMA patient fibroblasts
Life Sci Alliance. 2019 Mar 25;2(2):e201800268
HEK293 cells
1, 5, 10, 50, 100 µM
2 days
Z-FA-FMK significantly increased SMN protein expression in a dose-dependent manner
Life Sci Alliance. 2019 Mar 25;2(2):e201800268
293T cells
0.1 to 100 µM
30 hours
To evaluate the inhibitory effect of Z-FA-FMK on SARS-CoV-2 3CLpro, results showed that Z-FA-FMK significantly inhibited 3CLpro activity with an EC50 of 26.3 µM and no significant cytotoxicity.
Viruses. 2021 Jan 24;13(2):173
Human CD8+ T cells
50 µM
4 hours
Under anti-CD3 stimulation, Z-FA-FMK induced death in human CD8+ T cells.
J Exp Med. 2002 Aug 19;196(4):493-503
Mouse CD8+ T cells
50 µM
4 hours
Under anti-CD3 stimulation, Z-FA-FMK induced 35-55% cell death, while control compounds GF-DMK and ZFβA-FMK did not show this effect.
J Exp Med. 2002 Aug 19;196(4):493-503
SKBR-3 cells
20 µM
4 hours
Used as a negative control for caspase inhibitor to verify the specificity of Z-DEVD-FMK. Results showed Z-FA-FMK did not affect 13-MTD-induced apoptosis.
Lipids Health Dis. 2005 Nov 23;4:29
SMA patient iPSCs
1, 10, 100 µM
48 hours
Z-FA-FMK significantly increased SMN protein expression in SMA iPSCs
Life Sci Alliance. 2019 Mar 25;2(2):e201800268
Vero E6 cells
11.39 µM
72 hours
Evaluate anti-SARS-CoV-2 viral infection activity; results showed Z-FA-FMK could inhibit virus-induced cytopathic effect with EC50 of 0.13 μM
Z-FA-FMK significantly increased functional SMN protein expression and reduced motor neuron apoptosis
Life Sci Alliance. 2019 Mar 25;2(2):e201800268
Z-FA-FMK 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
NOX2-deficient mice (Ncf1-/-)
Intravenous injection
160 μg/mouse
3 hours before serum injection on day 0 and on day 4
To investigate the effect of Z-FA-FMK on the severity of serum-induced arthritis in NOX2-deficient mice. Results showed that Z-FA-FMK effectively suppressed the severity of arthritis, particularly under conditions lacking ROS regulation.
Antioxid Redox Signal. 2015 Oct 20;23(12):973-84
Mice
SMNΔ7 mouse model
Intracerebroventricular injection
60 ng
Once daily from PND1 to PND3
Z-FA-FMK significantly elevated SMN protein levels in spinal cord and increased the number of motor neurons in the lumbar spinal cord
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