Z-LEHD-FMK
Z-LEHD-FMK (CAS 210345-04-3) is a selective, irreversible inhibitor targeting caspase-9, an initiator caspase critical to mitochondria-mediated apoptosis. Caspase-9 activation leads to downstream cleavage of procaspase-3 and procaspase-7. Experimentally, Z-LEHD-FMK inhibits TRAIL-induced apoptosis in models including human colon cancer cells (HCT116), kidney cells (HEK293), and normal hepatocytes, suggesting selective cytoprotection of normal tissues. Additionally, in vivo studies demonstrate neuroprotection, as indicated by improved neurological outcomes following ischemia/reperfusion injury and spinal cord trauma.
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| Storage | Store at -20°C |
| M.Wt | 690.72 |
| Cas No. | 210345-04-3 |
| Formula | C32H43FN6O10 |
| Solubility | insoluble in H2O; ≥107.4 mg/mL in DMSO; ≥98.2 mg/mL in EtOH |
| Chemical Name | methyl (4S)-5-[[(2S)-1-[[(3S)-5-fluoro-1-methoxy-1,4-dioxopentan-3-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoate |
| SDF | Download SDF |
| Canonical SMILES | CC(C)CC(C(=O)NC(CCC(=O)OC)C(=O)NC(CC1=CN=CN1)C(=O)NC(CC(=O)OC)C(=O)CF)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 |
Human colon cancer, HCT116, human embryonic fibroblastand 293 cell lines |
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Preparation method |
Soluble in DMSO > 10 mM. 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. |
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Reaction Conditions |
20 μM Z-LEHD-FMK for 30 mins followed by 20ng/ml TRAIL for 4 hours |
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Applications |
Z-LEHD-FMK completely protects HCT116 and 293 cells from TRAIL-induced toxicity. Z-LEHD-FMK also protected human hepatocytes from TRAIL-induced apoptosis. The colony growth of HCT116 is reduced in the presence of TRAIL, and there are significantly more colonies present when the HCT116 cells were incubated in the presence of TRAIL and Z-LEHD-FMK. |
| Animal experiment [2]: | |
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Animal models |
Adult male Wistar albino rats, 250 to 350 g, spinal cord injury model |
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Dosage form |
Intravenous 0.8-mM/kg injection of z-LEHD-fmk. |
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Preparation method |
Dry-form z-LEHD-fmk was dissolved in dimethylsulfoxide prepared with phosphatebuffered saline. |
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Applications |
At 24 hours post-injury, the mean apoptotic cell count in trauma-only controls was significantly higher than that in z-LEHD-fmk–treated group. Electron microscopy results also show Z-LEHD-FMK treatment protected neurons, glia, myelin, axons, and intracellular organelles. The specimens treated with z-LEHD-fmk displays significantly fewer apoptotic cells and diminished axonal demyelination. |
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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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References: 1. Ozoren N, Kim K, Burns TF, 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 Res, 2000, 60(22): 6259-6265. 2. Colak A, Karao lan A, Barut S, et al. Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury. J Neurosurg Spine, 2005, 2(3): 327-334. |
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Quality Control & MSDS
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