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Ac-DMLD-CMK

Cat No.:V128076 Purity: ≥98%
Ac-DMLD-CMK is a caspase 3 inhibitor and a GSDME inhibitor.
Ac-DMLD-CMK
Ac-DMLD-CMK Chemical Structure CAS No.: 2588354-33-8
Product category: Caspase
This product is for research use only, not for human use. We do not sell to patients.
Size Price
500mg
1g
Other Sizes
Official Supplier of:
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Product Description
Ac-DMLD-CMK is a caspase 3 inhibitor and a GSDME inhibitor. Ac-DmLD-CMK binds directly to the catalytic domain of caspase-3, blocking caspase-3-mediated GSDME cleavage, inhibiting the activation of caspase-3 and GSDME in the caspase-3-GSDME signaling pathway, and reducing pyroptosis and apoptosis levels, as well as the expression of LDH, IL-6, IL-1β, and IL-18. Ac-DmLD-CMK can alleviate renal function deterioration, renal tubular epithelial cell damage, inflammatory cytokine secretion, lung structural damage, and chemotherapy-induced nephrotoxicity.
Biological Activity I Assay Protocols (From Reference)
ln Vitro
Ac-DMLD-CMK (5 μM; 6 hours pre-incubation) inhibited simvastatin-induced pyroptosis and decreased cell viability in MGC-803 human gastric cancer cells [3].
ln Vivo
Ac-DMLD-CMK (5 mg/kg/day; intraperitoneal injection; single injection 1 hour before cisplatin administration) can inhibit the activation of caspase 3 and GSDME, alleviate renal function deterioration in cisplatin-induced acute kidney injury in male C57BL/6 mice, reduce renal tubular epithelial damage, and reduce the secretion of inflammatory cytokines [1]. Ac-DMLD-CMK (5 mg/kg; intraperitoneal injection; single administration 3 hours before cecal ligation and perforation (CLP)) can significantly alleviate CLP-induced acute lung injury in male C57BL/6J mice by inhibiting caspase-3/GSDME-mediated pyroptosis and apoptosis, as evidenced by a decrease in lung injury score, inflammatory mediator levels, and cell death markers [2].
Animal Protocol
Animal/Disease Models:C57BL/6 (male, 6-8 weeks old, 20-25 g, cisplatin-induced) [1]
Doses: 5 mg/kg/day
Route of Administration: Intraperitoneal injection; single injection 1 hour before cisplatin administration
Experimental Results: Compared with mice treated with cisplatin alone, serum creatinine and blood urea nitrogen levels were reduced. Renal tubular epithelial cell death was reduced. The levels of cleaved Gsdme (Gsdme-N) and cleaved caspase 3 were reduced in mice, but had no significant effect on full-length Gsdme (Gsdme-FL). The mRNA expression of Ngal, Il6, Tnfa and Il1b in the kidneys was inhibited; the expression of Kim1 was not affected.
Animal/Disease Models:C57BL/6J (male, 6-8 weeks old, sepsis model induced by cecal ligation and perforation) [2]
Doses: 5 mg/kg
Route of Administration: Intraperitoneal injection; single administration (3 hours before cecal ligation and perforation)
Experimental Results: Compared with the cecal ligation and perforation group, the lung coefficient was reduced. Lung histopathology was improved, with reduced alveolar wall thickening, congestion, hemorrhage and inflammatory cell infiltration, and a lower lung injury score. Lung ultrastructural damage was reduced, including type II alveolar epithelial cell edema, mitochondrial structural damage and reduced lamellar body vacuolation. Compared with the cecal ligation and perforation group, the protein expression of GSDME-N and cleaved-caspase-3 in lung tissue was reduced. Compared with the CLP group, the mean fluorescence intensity of GSDME in lung tissue was reduced. Compared with the CLP group, caspase-3 activity in lung tissue was decreased. Serum lactate dehydrogenase (LDH) and interleukin-6 (IL-6) levels were decreased compared with the CLP group. The proportion of TUNEL-positive cells in lung tissue was decreased compared with the CLP group. Cleaved-PARP protein expression was decreased in lung tissue compared with the CLP group. IL-18 and IL-1β protein expression were decreased in lung tissue compared with the CLP group. Levels of pro-caspase-1, caspase-1, pro-IL-1β, and IL-1β were decreased in lung tissue compared with the CLP group.
References

[1]. Caspase 3/GSDME-dependent pyroptosis contributes to chemotherapy drug-induced nephrotoxicity. Cell Death Dis. 2021;12(2):186. Published 2021 Feb 15.

[2]. Inhibiting caspase-3/GSDME-mediated pyroptosis ameliorates septic lung injury in mice model. Mol Immunol. 2024;172:96-104.

[3]. Antitumor Effect of Simvastatin in Combination With DNA Methyltransferase Inhibitor on Gastric Cancer via GSDME-Mediated Pyroptosis. Front Pharmacol. 2022;13:860546. Published 2022 Apr 20.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C22H35CLN4O9S
Molecular Weight
567.05
CAS #
2588354-33-8
Sequence
Ac-Asp-Met-Leu-{Asp-CMK}Ac-DML-{Asp-CMK}
SequenceShortening
Ac-DML-{Asp-CMK}
Appearance
Typically exists as solids at room temperature
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.7635 mL 8.8176 mL 17.6351 mL
5 mM 0.3527 mL 1.7635 mL 3.5270 mL
10 mM 0.1764 mL 0.8818 mL 1.7635 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.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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