| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SDZ 224-015 targets multiple enzymes and receptors. It is a potent inhibitor of interleukin-1 beta (IL-1β) converting enzyme (ICE) and caspase-1. By inhibiting these enzymes, it blocks the maturation and secretion of the pro-inflammatory cytokine IL-1β. Additionally, it targets the main protease (Mpro) of SARS-CoV-2 with an IC50 of 30 nM. It also acts as a leukotriene B4 (LTB4) receptor inhibitor, blocking LTB4-mediated chemotaxis.
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| ln Vitro |
In vitro, SDZ 224-015 demonstrates potent inhibitory activity against ICE/caspase-1 and SARS-CoV-2 Mpro. It has an IC50 of 30 nM against Mpro. Its activity is typically assessed in enzyme inhibition assays using purified enzymes. The compound's ability to inhibit IL-1β production is confirmed in cell-based assays. It also serves as a non-nucleoside analog for studying reverse transcriptase catalytic blocking.
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| ln Vivo |
Carrageenin-induced paw oedema is potently reduced by SDZ 224-015 (0.3-300 μg/kg)[2]. In the Randall-Selitto yeast-inflamed paw pressure test, SDZ 224-015 (0.2–5 mg/kg, po) exhibits analgesic efficacy; this effect becomes significant at 1 mg/kg[2].
In vivo, SDZ 224-015 has robust oral activity in classic rodent inflammation models. It reduces carrageenan-induced paw edema in rats, confirming its anti-inflammatory activity. Its inhibition of ICE/caspase-1 leads to reduced IL-1β production, which is a key mediator of inflammation. The compound's oral activity established ICE as a druggable target and laid the groundwork for subsequent generations of clinical-stage caspase-1 inhibitors. |
| Enzyme Assay |
For non-cellular enzyme/receptor binding studies, SDZ 224-015's activity is evaluated in enzyme inhibition assays. Purified ICE/caspase-1 or SARS-CoV-2 Mpro is incubated with a substrate and varying concentrations of the compound. Enzyme activity is measured, and IC50 values are calculated from the dose-response curves. Its activity as a leukotriene B4 receptor inhibitor can also be assessed in receptor binding assays.
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| Cell Assay |
For in vitro cellular experiments, immune cells such as macrophages are cultured and stimulated to produce IL-1β. The cells are treated with SDZ 224-015 at various concentrations, and the amount of IL-1β produced is measured by ELISA. The compound's ability to inhibit IL-1β production confirms its activity as an ICE/caspase-1 inhibitor. Cytotoxicity is assessed in parallel using standard cell viability assays.
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| Animal Protocol |
In vivo animal studies for SDZ 224-015 are conducted in rodent models of inflammation. The compound is administered orally at various doses, and its anti-inflammatory effect is assessed by measuring paw edema in the carrageenan-induced paw edema model. The compound's robust oral activity in these models established ICE as a druggable target and laid the groundwork for subsequent generations of clinical-stage caspase-1 inhibitors.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SDZ 224-015 are not extensively detailed in the provided sources. It has a molecular weight of 652.52 and is a peptide designed for investigating structural determinants of receptor-interaction motifs. Its robust oral activity in rodent models suggests it has good oral bioavailability. Comprehensive pharmacokinetic studies are needed to fully characterize its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
The toxicity profile of SDZ 224-015 is not explicitly detailed in the provided sources. As a research compound, standard laboratory safety precautions should be followed when handling it. It is intended for research use only and is not for human therapeutic applications. Its safety would be evaluated in the context of its development as an anti-inflammatory or antiviral agent.
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| References |
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| Additional Infomation |
SDZ 224-015 is an orally active inhibitor of ICE/caspase-1 and SARS-CoV-2 Mpro. It has a molecular weight of 652.52 and exhibits anti-inflammatory activity, reducing carrageenan-induced paw edema in rats. It also targets Mpro with an IC50 of 30 nM. This research compound is for laboratory use only and has not been approved for clinical applications.
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| Molecular Formula |
C30H35CL2N3O9
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|---|---|
| Molecular Weight |
652.5196
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| Exact Mass |
651.175
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| CAS # |
161511-45-1
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| PubChem CID |
10189783
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| Appearance |
White to off-white solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
44
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| Complexity |
996
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CCOC(=O)C[C@@H](C(=O)COC(=O)C1=C(C=CC=C1Cl)Cl)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)OCC2=CC=CC=C2
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| InChi Key |
VMKPCENEHPIWJT-DOPYIHRPSA-N
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| InChi Code |
InChI=1S/C30H35Cl2N3O9/c1-5-42-24(37)14-22(23(36)16-43-29(40)25-20(31)12-9-13-21(25)32)34-27(38)18(4)33-28(39)26(17(2)3)35-30(41)44-15-19-10-7-6-8-11-19/h6-13,17-18,22,26H,5,14-16H2,1-4H3,(H,33,39)(H,34,38)(H,35,41)/t18-,22-,26-/m0/s1
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| Chemical Name |
[(3S)-5-ethoxy-3-[[(2S)-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-2,5-dioxopentyl] 2,6-dichlorobenzoate
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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 : 100 mg/mL (153.25 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5325 mL | 7.6626 mL | 15.3252 mL | |
| 5 mM | 0.3065 mL | 1.5325 mL | 3.0650 mL | |
| 10 mM | 0.1533 mL | 0.7663 mL | 1.5325 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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