Description
Tetromycin B is a cysteine protease inhibitor with K
i values of 0.62, 1.42, 32.5, and 1.59 μM for rhodesain, falcipain-2, cathepsin L, and cathepsin B, respectively. It inhibits the growth of
T. brucei in vitro (IC
50 = 30.87 μM). Tetromycin B is also cytotoxic to HEK293T kidney cells and J774.1 macrophages (IC
50s = 71.77 and 20.2 μM, respectively).
Uses
Tetromycin B is an unusual tetronic acid, structurally related to kijanimicin, chlorothricin, saccharocarcin, tetrocarcin and versipelostatin. Tetromycin B has pronounced activity against antibiotic susceptible and resistant Gram positive bacteria including MRSA. Limited availability has restricted further investigation of this metabolite in the literature. Several members of this class have received considerable literature focus. Versipelostatin inhibits transcription from the promoter of GRP78, a gene that is activated as part of a stress signalling pathway under glucose deprivation resulting in unfolded protein response (UPR). The UPR-inhibitory action is seen only in conditions of glucose deprivation and causes selective and massive killing of the glucose-deprived cells. Tetrocarcin A appears to target the phosphatidylinositide-3'-kinase/Akt signalling pathway.
