Cycloheximide

2813474

Cycloheximide is an inhibitor of protein biosynthesis in eukaryotic organisms, with IC₅₀ of 532.5 nM and 2880 nM for protein synthesis and RNA synthesis in vivo, respectively.

IC50 & Target: IC50: 532.5 nM (protein synthesis), 2.88 uM (RNA synthesis)^[1]
In Vitro: Cycloheximide (CHX) is the most common laboratory reagent used to inhibit protein synthesis. Cycloheximide has been shown to block the elongation phase of eukaryotic translation. Cycloheximide binds the ribosome and inhibits eEF2-mediated translocation. Surprisingly, Cycloheximide allows one complete translocation cycle to proceed before halting any further elongation. Cycloheximide has been speculated that Cycloheximide requires an E-site bound deacylated tRNA for activity^[1].
In Vivo: The mice receive Cycloheximide injections at 30, 60, or 120 mg/kg prior to training with a 200 uA shock. There is a significant effect of Cycloheximide on latencies on the memory test trials (P<0.001). In saline controls, this shock level results in latencies on the test trial that are significantly higher than those at training. Injections of the lowest dose of Cycloheximide tested, 30 mg/kg, results in latencies on the test trial that are significantly higher than those seen in the saline control group. Mice receiving either of the two higher doses of Cycloheximide has latencies on the test trial that are comparable to those of the saline group, i.e., the higher doses neither enhanced nor impaired memory under these conditions, resulting in an inverted-U dose-response curve for Cycloheximide enhancement of memory^[2]. Infarct volume, as measured by morphometric analysis of infarct areas with triphenyl tetrazolium chloride (TTC), is significantly reduced by 92% and 61% when Cycloheximide is given 0 or 6 hr after HI respectively, but shows an insignificant trend in infarct reduction if Cycloheximide is administered 12 hr after hypoxia-ischemia (HI) compared to the HI control group, and no protective effect is observed when administration is delayed until 24 hr after HI^[3].

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