Description
Ac-YVAD-CHO is an inhibitor of caspase-1/interleukin-1β converting enzyme (ICE; K
i = 0.76 nM) and an acetylated form of the caspase-1 inhibitor YVAD-CHO . It is selective for caspase-1 over caspase-4, -5, -8, -9, and -10 (K
is = 163-970 nM), as well as over caspase-2, -3, -6, and -7 (K
is = >10,000 nM for all). It inhibits activation of caspase-1 and IL-1β in a cell-free assay using LPS-treated THP-1 cell homogenates when used at a concentration of 5 μM. Ac-YVAD-CHO (12.5 μmol/kg) reduces pancreatic levels of IL-18 and serum levels of IL-1β, as well as reduces pyroptosis of pancreatic cells, in a mouse model of cerulein-induced acute pancreatitis but does not decrease pancreatic expression of NOD-like receptor protein 3 (NLRP3). It increases susceptibility to lethal
E. coli infection but prevents LPS-induced death in C3H/HeN mice when administered at doses of 5 and 10 mg/kg, respectively.
Uses
A potent, specific, and reversible inhibitor of caspases-1, -4 and -5
References
[1] CHAPMAN K T. Synthesis of a potent, reversible inhibitor of interleukin-1β converting enzyme[J]. Bioorganic & Medicinal Chemistry Letters, 1992, 2 6: Pages 613-618. DOI:
10.1016/s0960-894x(01)81209-9[2] JOHN G WALSH. Caspase-1 promiscuity is counterbalanced by rapid inactivation of processed enzyme.[J]. The Journal of Biological Chemistry, 2011: 32513-32524. DOI:
10.1074/jbc.m111.225862[3] JIANHUA WANG . Cathepsin B aggravates acute pancreatitis by activating the NLRP3 inflammasome and promoting the caspase-1-induced pyroptosis[J]. International immunopharmacology, 2021, 94: Article 107496. DOI:
10.1016/j.intimp.2021.107496[4] VISHWAS D JOSHI. Role of caspase 1 in murine antibacterial host defenses and lethal endotoxemia.[J]. Infection and Immunity, 2002, 70 12: 6896-6903. DOI:
10.1128/iai.70.12.6896-6903.2002
