Z-FA-FMK
Z-FA-FMK is a control peptidic fluoromethylketone (boc-Thr-CH2F), and inhibitor to calpain (Ac-Leu-Leu-norleucinal), cathepsin B (Z-Phe-Ala-CH2F), and CPP32-like proteases (Z-DEVD-CH2F) [1]. A peptidyl fluoromethyl ketone (cathepsin B) was found to be an effective compound in a time dependent inactivation of cathepsin B isozymes from a number of tissues including human tumors [2]. The inhibitor of cathepsins B and L Z-FA-fmk blocks the induction of DEVDase activity, DNA fragmentation, and externalization of phosphatidylserine by selective RRMs. Z-FA-FMK can inhibit caspase activity in vitro and selectively inhibits recombinant effector caspases 2, -3, -6, and -7. In contrast, purified initiator caspases 8 and 10 are not affected, whereas the apoptosome-associated caspase 9 is only partially inhibited by Z-FA-FMK in vitro. [3]
It is an inhibitor of cysteine proteases, such as cathepsin B, which do not require a P1 Asp residue. It may be used as a negative control inhibitor for FMK P1 Asp caspase inhibitors.
References:
1. Inhibition of the interleukin-1 beta converting enzyme family rescues neurons from apoptotic death. Lynch, T., Vasilakos, J.P., Raser, K., Keane, K.M., Shivers, B.D. Mol. Psychiatry (1997)
2. Visualization of time-dependent inactivation of human tumor cathepsin B isozymes by a peptidyl fluoromethyl ketone using a fluorescent print technique. Smith, R.E., Rasnick, D., Burdick, C.O., Cho, K.J., Rose, J.C., Vahratian, A. Anticancer Res. (1988)
3. Lopez-Hernandez, F. J., Ortiz, M. A., Bayon, Y., & Piedrafita, F. J. (2003). Z-FA-fmk Inhibits Effector Caspases but not Initiator Caspases 8 and 10, and Demonstrates That Novel Anticancer Retinoid-related Molecules Induce Apoptosis via the Intrinsic Pathway1. Molecular cancer therapeutics, 2(3), 255-263.
- 1. Zhijun Liu, Himani Nailwal, et al. "A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation." Immunity. 2021 Feb 9;54(2):247-258.e7. PMID: 33444549
- 2. Mohammed Mohasin, Katharin Balbirnie-Cumming, et al. "Macrophages utilize mitochondrial fission to enhance mROS production during responses to Streptococcus pneumoniae." bioRxiv. 2019 August 02.
- 3. Hodges AL, Kempen CG, et al. "TNF Family Cytokines Induce Distinct Cell Death Modalities in the A549 Human Lung Epithelial Cell Line when Administered in Combination with Ricin Toxin." Toxins (Basel). 2019 Aug 1;11(8). pii: E450. PMID: 31374990
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 386.42 |
| Cas No. | 105637-38-5;197855-65-5 |
| Formula | C21H23N2O4F |
| Synonyms | Z-FA-FMK, Z-Phe-Ala-fluoromethyl ketone, Z-Phe-Ala-FMK, Zfa-FMK, Z-Phe-Ala-CH2F, Cathepsin B, Caspase Inhibitor |
| Solubility | insoluble in H2O; ≥13.45 mg/mL in DMSO; ≥3.57 mg/mL in EtOH with ultrasonic |
| Chemical Name | benzyl N-[1-[(4-fluoro-3-oxobutan-2-yl)amino]-1-oxo-3-phenylpropan-2-yl]carbamate |
| SDF | Download SDF |
| Canonical SMILES | CC(C(=O)CF)NC(=O)C(CC1=CC=CC=C1)NC(=O)OCC2=CC=CC=C2 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
Jurkat T cells |
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Reaction Conditions |
5, 30, or 100 μM Z-FA-FMK for 1 h preincubation |
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Applications |
Increasing concentrations of Z-FA-FMK prevented retinoid-related molecule (RRM)-induced DNA fragmentation and DEVDase activity. Similarly, preincubation with a high concentration of Z-FA-FMK (100 μM) significantly inhibited the externalization of phosphatidylserine induced by RRMs. Z-FA-FMK, as an inhibitor of cathepsins B and L, has been used to explore the molecular mechanism underlying the anticancer activity of RRMs. |
| Animal experiment:[2] | |
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Animal models |
SCID mice xenografted with Ras oncogenic HT1080 cells |
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Dosage form |
0.02 mg Administered intratumorally, everyday up to 7 days post-viral injection and every 2 days until completion of the experiment. |
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Applications |
Z-FA-FMK effectively blocked the replication activity of respiratory enteric orphan (reo)virus in both tumor and hear tissues. Therefore, Z-FA-FMK could serve as a potential viral inhibitor which prevents reovirus-mediated myocarditis and oncolysis in vivo. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Lopez-Hernandez FJ, Ortiz MA, Bayon Y, et al. Z-FA-fmk inhibits effector caspases but not initiator caspases 8 and 10, and demonstrates that novel anticancer retinoid-related molecules induce apoptosis via the intrinsic pathway. Molecular Cancer Therapeutics, 2003, 2(3): 255-263. 2. Kim M, Hansen KK, Davis L, et al. Z-FA-FMK as a novel potent inhibitor of reovirus pathogenesis and oncolysis in vivo. Antiviral Therapy, 2010, 15(6): 897-905. |
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| Description | Z-FA-FMK is an irreversible inhibitor of cysteine protease | |||||
| Targets | cysteine protease | |||||
| IC50 | ||||||
Quality Control & MSDS
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Chemical structure
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