1. Apoptosis Immunology/Inflammation
  2. Caspase Pyroptosis
  3. Ac-DMLD-CMK

Ac-DmLD-CMK is a caspase 3 inhibitor and a GSDME inhibitor. Ac-DmLD-CMK binds directly to the catalytic domain of caspase-3, blocks caspase-3-mediated cleavage of GSDME, inhibits the activation of caspase 3 and Gsdme in the caspase 3-Gsdme signaling pathway, and reduces the levels of pyroptosis and apoptosis as well as the expression of LDH, IL-6, IL-1β and IL-18. Ac-DmLD-CMK alleviates renal function deterioration, renal tubular epithelial cell injury, inflammatory cytokine secretion, pulmonary structural damage, and chemotherapy-induced nephrotoxicity.

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Ac-DMLD-CMK

Ac-DMLD-CMK Chemical Structure

CAS No. : 2588354-33-8

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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, blocks caspase-3-mediated cleavage of GSDME, inhibits the activation of caspase 3 and Gsdme in the caspase 3-Gsdme signaling pathway, and reduces the levels of pyroptosis and apoptosis as well as the expression of LDH, IL-6, IL-1β and IL-18. Ac-DmLD-CMK alleviates renal function deterioration, renal tubular epithelial cell injury, inflammatory cytokine secretion, pulmonary structural damage, and chemotherapy-induced nephrotoxicity[1][2][3].

IC50 & Target

Caspase 3

 

In Vitro

Ac-DMLD-CMK (5 μM; 6 h pre-incubation) inhibits simvastatin-induced pyroptosis and cell viability reduction in MGC-803 human gastric cancer cells[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Ac-DMLD-CMK (5 mg/kg/day; i.p.; single injection 1 hour prior to cisplatin administration) inhibits caspase 3 and Gsdme activation, alleviates kidney function deterioration, reduces renal tubular epithelial injury, and lowers inflammatory cytokine secretion in cisplatin-induced acute kidney injury in male C57BL/6 mice[1].
Ac-DMLD-CMK (5 mg/kg; i.p.; single dose 3 h pre-CLP) significantly reduces CLP-induced acute lung injury in male C57BL/6 J mice by inhibiting caspase-3/GSDME-mediated pyroptosis and apoptosis, as evidenced by reduced lung injury scores, inflammatory mediator levels, and cell death markers[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 (male, 6-8 weeks old, 20-25 g, cisplatin-induced)[1]
Dosage: 5 mg/kg/day
Administration: i.p.; single injection 1 hour prior to cisplatin administration
Result: Reduced serum creatinine and blood urea nitrogen levels compared to cisplatin-only treated mice.
Alleviated renal tubular epithelial cell death.
Reduced levels of cleaved mouse Gsdme (Gsdme-N) and cleaved caspase 3, with no significant effect on full-length mouse Gsdme (Gsdme-FL).
Suppressed renal mRNA expression of Ngal, Il6,Tnfa, and Il1b; did not affect Kim1 expression.
Animal Model: C57BL/6 J (male, 6-8 weeks old, CLP-induced sepsis model)[2]
Dosage: 5 mg/kg
Administration: i.p.; single dose (3 h before CLP surgery)
Result: Reduced lung coefficient relative to CLP group.
Improved lung histopathology, with reduced alveolar wall thickening, congestion, bleeding, and inflammatory cell infiltration, and decreased lung injury score relative to CLP group.
Attenuated ultrastructural lung damage, including reduced type II alveolar epithelial cell edema, mitochondrial structural damage, and lamellar body vacuolization relative to CLP group.
Decreased protein expression of GSDME-N and cleaved-caspase-3 in lung tissue relative to CLP group.
Reduced mean fluorescence intensity of GSDME in lung tissue relative to CLP group.
Decreased caspase-3 activity in lung tissue relative to CLP group.
Reduced serum lactate dehydrogenase (LDH) and interleukin-6 (IL-6) levels relative to CLP group.
Decreased proportion of TUNEL-positive cells in lung tissue relative to CLP group.\nDecreased protein expression of cleaved-PARP in lung tissue relative to CLP group
nDecreased protein expression of IL-18 and IL-1β in lung tissue relative to CLP group.
Decreased lung tissue levels of pro-caspase-1, caspase-1, pro-IL-1β, and IL-1β relative to CLP group.
Molecular Weight

567.05

Formula

C22H35ClN4O9S

CAS No.
Sequence

Ac-Asp-Met-Leu-{Asp-CMK}

Sequence Shortening

Ac-DML-{Asp-CMK}

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Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Ac-DMLD-CMK
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HY-P10939
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