ac-YVAD-cmk

Ac-YVAD-CMK is a cell-permeable, irreversible peptide-based inhibitor of Caspase-1 (interleukin-1beta converting enzyme, ICE). It consists of the tetrapeptide sequence Tyr-Val-Ala-Asp (YVAD) capped with an N-terminal acetyl group and a C-terminal chloromethyl ketone (CMK) warhead. The CMK group facilitates covalent binding to the active site cysteine of Caspase-1, thereby blocking the maturation of pro-inflammatory cytokines IL-1beta and IL-18 and inhibiting gasdermin D (GSDMD)-mediated pyroptotic cell death. Widely used as a pharmacological probe in preclinical research, it has demonstrated efficacy in models of ischemic stroke, lupus nephritis, sepsis-induced lung injury, and various inflammatory conditions. However, its clinical translation is limited by metabolic fragility, broad caspase cross-reactivity, and poor pharmacokinetic properties, leading to its primary use as a foundational chemical template for the design of more selective, clinically viable therapeutics.

Other names

Caspase-1 Inhibitor ICaspase1 Inhibitor ICaspase 1 Inhibitor IN-acetyl-Tyr-Val-Ala-Asp-chloromethylketoneN-acetyl-L-tyrosyl-L-valyl-L-alanyl-L-aspartyl-chloromethylketone