Uses
Ac-FLTD-CMK, a gasdermin D (GSDMD)-derived inhibitor, is a specific inflammatory caspases inhibitor. Ac-FLTD-CMK is effective against caspases-1 (IC50 of 46.7 nM), caspases-4 (IC50 of 1.49 μM), caspases-5 (IC50 of 329 nM), and caspases-11 , but not the apoptotic caspases such as caspase-3[1].
Biological Activity
Ac-FLTD-CMK is a selective gasdermin D (GSDMD) clevage inhibitor (IC50 = 46.7 nM, 329 nM, 1.49 μM, respectively, against GSDMD clevage by human caspase-1, -5, -4 in cell-free enzymatic assays) th at suppresses pyroptosis downstream of both canonical and noncanonical inflammasomes, as well as reduces IL-1β release following activation of the NLRP3 inflammasome in macrophages (10 μM 4h post 200 ng/mL LPS and 0.5h before ATP or nigericin). Ac-FLTD-CMK selectively blocks GSDMD clevage by inflammatory caspases without affecting apoptotic caspases (caspase-3 IC50 >100 μM) or apoptosis.
IC 50
Caspase-1: 46.7 nM (IC
50); Caspase-4: 1.49 μM (IC
50); Caspase-5: 329 nM (IC
50); Caspase-11
References
[1] Jie Yang, et al. Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6792-6797. DOI:
10.1073/pnas.1800562115
