| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Caspase-9
Caspase-9 Inhibitor III targets caspase-9, a key initiator caspase in the intrinsic (mitochondrial) apoptotic pathway. The compound is a potent and irreversible inhibitor of caspase-9. It is cell-permeable and peptide-based (Ac-LEHD-cmk). By inhibiting caspase-9, the compound blocks the activation of downstream effector caspases (caspase-3 and caspase-7), thereby preventing apoptosis. |
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| ln Vitro |
Catapase-9 Inhibitor III (0.07-0.105 μM; perfusion 10 min) markedly reduced the release of lactate dehydrogenase and creatine kinase in coronary wastewater, the apoptosis index, and the rise in infarct size in isolated rat hearts caused by I/R[1]. MMP-2-induced troponin I hydrolysis is inhibited by Caspase-9 Inhibitor III (30 μM) [2].
In vitro studies demonstrate that Caspase-9 Inhibitor III (Ac-LEHD-cmk) is a potent and irreversible inhibitor of caspase-9. The compound is cell-permeable. It exhibits protective effects against ischemia-reperfusion-induced myocardial injury in isolated rat heart models. At concentrations of 0.07-0.105 μM, the compound reduces the apoptotic index of isolated rat heart. It markedly reduces the release of lactate dehydrogenase and creatine kinase in coronary wastewater. |
| ln Vivo |
In vivo, Caspase-9 Inhibitor III exhibits protective effects on ischemia-reperfusion-induced myocardial injury. The compound reduces myocardial infarct size during reperfusion (~70 nM). It markedly reduces the release of lactate dehydrogenase and creatine kinase, the apoptosis index, and the rise in infarct size in isolated rat hearts. The compound's protective effects are mediated through inhibition of caspase-9 and blockade of the intrinsic apoptotic pathway.
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| Enzyme Assay |
The caspase-9 inhibitory activity of Caspase-9 Inhibitor III can be assessed using in vitro enzyme assays. In a typical assay, recombinant caspase-9 is incubated with a fluorogenic substrate (such as Ac-LEHD-AFC) and varying concentrations of the inhibitor. The cleavage of the substrate releases a fluorescent product that is measured, and the IC50 is calculated. The compound is a potent and irreversible inhibitor. The specificity for caspase-9 over other caspases can be assessed using similar assays with other caspase isoforms.
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| Cell Assay |
The cellular activity of Caspase-9 Inhibitor III is assessed using cell-based apoptosis assays. Cells are treated with apoptosis-inducing agents (such as staurosporine or UV irradiation) in the presence or absence of the inhibitor. Apoptosis is assessed by measuring caspase-3/7 activity, annexin V/propidium iodide staining, or detecting cleaved PARP. The compound's ability to inhibit caspase-9 and block apoptosis is measured. The compound is cell-permeable.
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| Animal Protocol |
Caspase-9 Inhibitor III has been evaluated in isolated rat heart models of ischemia-reperfusion injury. In these studies, hearts are perfused with the inhibitor at concentrations of 0.07-0.105 μM. Myocardial infarct size, lactate dehydrogenase release, creatine kinase release, and apoptotic index are measured. The compound reduces infarct size and apoptosis. These findings demonstrate its cardioprotective effects.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data has been published for Caspase-9 Inhibitor III. The compound has a molecular weight of 587.02 g/mol and a molecular formula of C25H39N7O10. It is soluble in DMSO at 125 mg/mL. The compound is cell-permeable. Further studies would be needed to characterize its absorption, distribution, metabolism, and excretion properties.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for Caspase-9 Inhibitor III. As a caspase-9 inhibitor, it may have effects on apoptosis in normal tissues. The compound has shown protective effects in ischemia-reperfusion injury models. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development. The compound is intended for research use only.
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| References |
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| Additional Infomation |
Caspase-9 Inhibitor III (Ac-LEHD-cmk, CAS# 403848-57-7) is a potent and irreversible cell-permeable inhibitor of caspase-9. It exhibits protective effects against ischemia-reperfusion-induced myocardial injury, reducing infarct size (~70 nM) and apoptosis. The compound markedly reduces lactate dehydrogenase and creatine kinase release in isolated rat hearts. It has a molecular weight of 587.02 g/mol and a molecular formula of C25H39N7O10. The compound is used in apoptosis and cardiovascular research.
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| Molecular Formula |
C24H35CLN6O9
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|---|---|
| Molecular Weight |
587.022505044937
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| Exact Mass |
586.215
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| CAS # |
403848-57-7
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| PubChem CID |
16760347
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| Appearance |
White to off-white solid powder
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| LogP |
-0.7
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
40
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| Complexity |
948
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| Defined Atom Stereocenter Count |
4
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| SMILES |
ClCC([C@H](CC(=O)O)NC([C@H](CC1=CN=CN1)NC([C@H](CCC(=O)O)NC([C@H](CC(C)C)NC(C)=O)=O)=O)=O)=O
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| InChi Key |
JSRLQUNMFYXVQD-XSLAGTTESA-N
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| InChi Code |
InChI=1S/C24H35ClN6O9/c1-12(2)6-17(28-13(3)32)23(39)29-15(4-5-20(34)35)22(38)31-18(7-14-10-26-11-27-14)24(40)30-16(8-21(36)37)19(33)9-25/h10-12,15-18H,4-9H2,1-3H3,(H,26,27)(H,28,32)(H,29,39)(H,30,40)(H,31,38)(H,34,35)(H,36,37)/t15-,16-,17-,18-/m0/s1
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| Chemical Name |
(4S)-4-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-carboxy-4-chloro-3-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 125 mg/mL (212.94 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7035 mL | 8.5176 mL | 17.0352 mL | |
| 5 mM | 0.3407 mL | 1.7035 mL | 3.4070 mL | |
| 10 mM | 0.1704 mL | 0.8518 mL | 1.7035 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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