Lactimidomycin

Lactimidomycin is a glutarimide-containing compound isolated from Streptomyces. Lactimidomycin is a potent inhibitor of eukaryotic translation elongation. Lactimidomycin has a potent antiproliferative effect on tumor cell lines and selectively inhibit protein translation. Lactimidomycin inhibits protein synthesis with an IC50 value of 37.82 nM. Lactimidomycin is also a potent and non-toxic inhibitor of dengue virus 2 and other RNA viruses. Anticancer and antiviral activities[1][2].

Lactimidomycin (0.01-100 nM; 24 hours; Hs 579T, HCC 1937, HCC 1395, HCC 2218, BT 474, MCF 7, MDA MB231 cells and MCF 10A) treatment inhibits cell growth with IC50 concentrations in the low nanomolar range, but higher doses are necessary to inhibit growth of the non-tumorigenic breast cell line MCF10A[1].Lactimidomycin induces a clear dose-responsive inhibition of DENV2 infectious particle production with an EC90 value of 0.4 μM. No measurable decrease in cell viability was detected at concentrations up to 12.5 µM[2].Lactimidomycin is a potent inhibitor of DENV2 and Lactimidomycin’s inhibition of DENV2 translation leads to reduced production of newly infectious particles. Lactimidomycin may protect cells from viral cytopathic effects including apoptosis, likely through inhibition of virus protein production and replication[2].

Lactimidomycin (0.6 mg/kg; intraperitoneal injection; daily; for one month; female nude mice) treatment has an appreciable effect on tumor growth in nude mice[1].

[1]. Schneider-Poetsch T, et al. Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol. 2010 Mar;6(3):209-217.
[2]. Carocci M, et al. Lactimidomycin is a broad-spectrum inhibitor of dengue and other RNA viruses. Antiviral Res. 2016 Apr;128:57-62.