Discovery of new benzhydrol biscarbonate esters as potent and selective apoptosis inducers of human melanomas bearing the activated ERK pathway: SAR studies on an ERK MAPK signaling modulator, ACA-28.

The recent discovery that an ERK signaling modulator [ACA-28 (2a)] preferentially kills human melanoma cell lines by inducing ERK-dependent apoptosis has generated significant interest in the field of anti-cancer therapy. In the first SAR study on 2a, here, we successfully developed candidates (2b, 2c) both of which induce more potent and selective apoptosis towards ERK-active melanoma cells than 2a, thus revealing the structural basis for inducing the ERK-dependent apoptosis and proposing the therapeutic prospect of these candidates against ERK-dependent cancers represented by melanoma.

Palladium-catalyzed synthesis of benzosilacyclobutenes via position-selective C(sp3)-H arylation.

A palladium-catalyzed synthesis of benzosilacyclobutenes has been developed via position-selective C(sp3)-H bond activation, including those having substituents at the methylene carbon on the 4-membered silacycle. The obtained products could be engaged in the palladium- or nickel-catalyzed ring-expansion reactions to give compounds possessing 6-membered silacycles.

Comparison Between Cz-C3/C4 and C3-C4 Montages to Protect Against Peripheral Stimulation in Transcranial Facial Motor-Evoked Potential Monitoring.

INTRODUCTION: In facial motor-evoked potential monitoring, efforts to reduce peripheral stimulation are necessary because it can cause false-negatives. The effects of peripheral stimulation on Cz-C3/C4 and C3-C4 montages were compared. METHODS: Facial motor-evoked potentials were recorded from bilateral orbicularis oculi (Oculi) and oris (Oris) muscles. The double-train approach combining single-pulse and five-train pulse stimulation was used to determine the effect of peripheral stimulation. If the five-train pulse produced a significant waveform, it was defined as "total success." In total success cases, "true success" was defined as a case in which no waveform appeared after the single pulse at the threshold level of the five-train pulse. The total and true success rates and the threshold value of Oculi and Oris were compared between Cz-C3/C4 and C3-C4 montages. RESULTS: Thirty-six muscles each of Oculi and Oris of 18 patients were used for the analysis. True success was more likely to be obtained by the Cz-C3/C4 montage than the C3-C4 montage in Oculi (42% vs. 22%, p = 0.039). Both Oculi and Oris had higher thresholds to elicit facial motor-evoked potentials with the Cz-C3/C4 montage (Oculi: 101.7 vs. 71.4 mA, p = 0.038; Oris: 94.8 vs. 73.1 mA, p = 0.016). CONCLUSIONS: Cz-C3/4 montage is more effective at reducing peripheral stimulation compared with the C3-4 montage. This effect was primarily seen in the orbicularis oculi muscle. It should be noted that the Cz-C3/C4 montage has a higher threshold than the C3-C4 montage in facial muscles. In facial motor-evoked potential monitoring, the Cz-C3/C4 montage may be more suitable to eliminate peripheral stimulation.