| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Z-Asp-CH2-DCB targets caspases, a family of cysteine proteases that play essential roles in apoptosis (programmed cell death), inflammation, and other cellular processes. It is a broad-spectrum caspase inhibitor with IC₅₀ values of 1.1 μM for caspase-3 and 4.1 μM for caspase-6. The compound irreversibly inhibits caspase activity by forming a covalent bond with the active site cysteine residue. It also inhibits proteases with caspase-like activity.
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| ln Vitro |
In a dose-dependent way, Z-Asp-CH2-DCB (10-100 μM) inhibits the production of IL-1β, TNF-α, IL-6, and IFN-γ in SEB-stimulated (200 ng; 16 h) PBMC. Additionally, there was an inhibition of MCP-1, MIP-1α, and MIP-1β chemokine production. On TSST-1-activated PBMC, Z-Asp-CH2-DCB had a comparable inhibitory impact, decreasing MCP-1, MIP-1α, TNF-α, IFN-γ, IL-1β, IL-6, and MIP-1β, in that order. 10%, 36%, 25%, 10%, 11%, 25%, and 30% of cell levels in the untreated state [1]. In PBMC treated with 200 ng SEB/ml, Z-Asp-CH2-DCB (10-100 μM; 48 hours) suppresses T cell proliferation [1].
In vitro, Z-Asp-CH2-DCB (10-100 μM) dose-dependently blocks the production of pro-inflammatory cytokines including IL-1β, TNF-α, IL-6, and IFN-γ in SEB-stimulated (200 ng) human peripheral blood mononuclear cells (PBMC). It reduces SEB-stimulated T-cell proliferation in a dose-dependent manner. The compound completely blocks S-nitrosoglutathione-induced apoptosis in macrophage and leukemic cell lines at 100 μM. It also prevents des-ring colchicine induced apoptosis of cells. |
| ln Vivo |
Z-Asp-CH2-DCB (1 mg; i.p.; every day for 3 weeks) inhibits the apoptosis of septal cells induced by SU5416 [1].
In vivo studies have demonstrated that Z-Asp-CH2-DCB prevents the development of severe pulmonary hypertension and intravascular pulmonary endothelial cell growth caused by chronic hypoxia in murine models. The compound prevents SU5416-induced pulmonary emphysema and apoptosis. It has been shown to reduce the rate of cleavage of Troponin I-C, an important component of the cardiac contractile apparatus. In renal ischemia-reperfusion models, the compound modulates calpain inhibitor protein calpastatin degradation. |
| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for Z-Asp-CH2-DCB involve caspase activity inhibition studies using recombinant human caspases. The assay typically uses a fluorogenic substrate (e.g., Ac-DEVD-AMC for caspase-3, Ac-VEID-AMC for caspase-6) that releases a fluorescent product upon cleavage by active caspase. Various concentrations of Z-Asp-CH2-DCB (typically 0.1-100 μM) are incubated with recombinant caspase and substrate in assay buffer (pH 7.4) at 37°C for 1-2 hours. Fluorescence is measured at excitation/emission wavelengths appropriate for AMC (360/460 nm). IC₅₀ values are calculated from dose-response curves by nonlinear regression. The irreversible nature of inhibition is confirmed by pre-incubation experiments where the compound is incubated with the enzyme before substrate addition.
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| Cell Assay |
Cell viability assay [1]
Cell Types: human peripheral blood mononuclear cells Tested Concentrations: 10, 50, 100 μM Incubation Duration: 48 hrs (hours) Experimental Results: T cell proliferation was inhibited in SEB-stimulated PBMC. For in vitro cell-based assays, human peripheral blood mononuclear cells (PBMC) or cell lines such as RAW 264.7 macrophages or U937 leukemic cells are cultured in appropriate media. Cells are treated with Z-Asp-CH2-DCB at concentrations ranging from 1-100 μM. For apoptosis studies, cells are exposed to apoptosis inducers (e.g., S-nitrosoglutathione, staurosporine) with or without compound pretreatment. Apoptosis is assessed by Annexin V-FITC/PI staining, caspase activity assays using fluorogenic substrates, and Western blot analysis of PARP cleavage. For cytokine production studies, PBMC are stimulated with SEB (200 ng) and cytokine levels in supernatants are measured by ELISA. T-cell proliferation is assessed by ³H-thymidine incorporation. |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (SU5416+ Z-Asp-CH2-DCB group) [1]
Doses: 1 mg Route of Administration: intraperitoneal (ip) injection; one time/day for 3 weeks Experimental Results: caspase in the lungs of SU5416-treated rats 3-like activity was Dramatically increased, while there was no increase in apoptotic activity in the lungs of rats treated with SU5416+Z-Asp-CH2-DCB. In vivo animal studies with Z-Asp-CH2-DCB typically use murine models. For pulmonary hypertension studies, mice or rats are exposed to chronic hypoxia (10% O₂) for 3-4 weeks with or without Z-Asp-CH2-DCB administration. The compound is administered via intraperitoneal injection at doses of 1-10 mg/kg daily. At study endpoint, right ventricular systolic pressure is measured, and lung tissues are collected for histopathological analysis of vascular remodeling. For renal ischemia-reperfusion studies, animals undergo renal artery clamping followed by reperfusion, with compound administered before or after ischemia. Tissue samples are processed for Western blot, immunohistochemistry, and TUNEL staining for apoptosis detection. |
| ADME/Pharmacokinetics |
Z-Asp-CH2-DCB is a cell-permeable compound. As a peptide-based inhibitor, it is expected to have moderate oral bioavailability and is typically administered via intraperitoneal or intravenous routes in preclinical studies. The compound has a molecular weight of 454.3 g/mol and is soluble in DMSO. Pharmacokinetic properties are characteristic of peptidomimetic compounds, with rapid clearance and distribution to tissues. The compound's irreversible binding to caspases contributes to its prolonged pharmacodynamic effects. Plasma protein binding and metabolic stability are typical of small peptide derivatives.
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| Toxicity/Toxicokinetics |
Z-Asp-CH2-DCB is considered to have a manageable toxicity profile at pharmacological doses. In cell-based assays, the compound shows activity at 1-100 μM without significant cytotoxicity at lower concentrations. In animal studies, the compound has been administered without major adverse effects at doses effective for caspase inhibition. As a caspase inhibitor, the compound may affect normal apoptotic processes, but this is typically well-tolerated in short-term studies. The compound has been used in numerous research studies and is not approved for human therapeutic use.
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| References |
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| Additional Infomation |
Z-Asp-CH2-DCB is a research tool widely used in apoptosis, inflammation, and cell death studies. Its broad-spectrum caspase inhibition makes it valuable for investigating the role of caspases in various biological processes. The compound has been used in studies of nitric oxide-induced apoptosis, hypoxia-induced necrosis of renal proximal tubules, and drug-induced apoptosis in leukemic cells. It has also been employed in studies of neutrophil differentiation and caspase-independent apoptosis pathways. The compound is not approved for clinical use and is intended for research purposes only.
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| Molecular Formula |
C20H17NO7CL2
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|---|---|
| Molecular Weight |
454.25748
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| Exact Mass |
453.038
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| Elemental Analysis |
C, 52.88; H, 3.77; Cl, 15.61; N, 3.08; O, 24.65
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| CAS # |
153088-73-4
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| PubChem CID |
9911778
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
674.2±55.0 °C at 760 mmHg
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| Flash Point |
361.6±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.594
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| LogP |
5.29
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
30
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| Complexity |
614
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=CC=C(C=C1)COC(=O)N[C@@H](CC(=O)O)C(=O)COC(=O)C2=C(C=CC=C2Cl)Cl
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| InChi Key |
FKJMFCOMZYPWCO-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C20H17Cl2NO7/c21-13-7-4-8-14(22)18(13)19(27)29-11-16(24)15(9-17(25)26)23-20(28)30-10-12-5-2-1-3-6-12/h1-8,15H,9-11H2,(H,23,28)(H,25,26)/t15-/m0/s1
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| Chemical Name |
(3S)-5-(2,6-dichlorobenzoyl)oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid
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| Synonyms |
Z-Asp-CH2-DCB; PASE-1 INHIBITOR V; FHN88734; FHN-88734; FHN 88734;
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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, avoid exposure to moisture. |
| 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 : ~100 mg/mL (~220.14 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.58 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 (4.58 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 (4.58 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 | 2.2014 mL | 11.0069 mL | 22.0138 mL | |
| 5 mM | 0.4403 mL | 2.2014 mL | 4.4028 mL | |
| 10 mM | 0.2201 mL | 1.1007 mL | 2.2014 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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