The SNP rs3792323 in MAPKAPK3 associates with the outcome of IFN therapy in patients with HCV genotype 1b. Our functional analyses indicate that MAPKAPK3 inhibits IFN-alfa-induced antiviral activity.

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Although only the first 24 hours of mucosal injury were observed in the present study, the most likely mechanisms by which monochloramine caused injury to the gastric mucosa appeared to be both oxidative damage and a reduction in blood flow, impairing the mucosal defense mechanism.

This study (NCT04369391) evaluated the effects of ulotaront (SEP‐363856), a novel trace amine‐associated receptor 1 (TAAR1) agonist in development for schizophrenia, on electrocardiogram parameters. Study design was a randomized, single‐dose, three‐period crossover (ulotaront 150 mg, placebo, moxifloxacin 400 mg). Sixty subjects with schizophrenia completed all periods. Ulotaront had no clinically relevant effect on heart rate, PR interval, or QRS duration. In by‐time‐point analysis (secondary analysis), the upper bound of the two‐sided 90% confidence interval for ΔΔQTcF (QT interval corrected for heart rate using Fridericia's formula) was below 10 ms at all time points for ulotaront. In concentration‐QTc analysis (primary analysis), a linear mixed‐effects model with ulotaront and its major metabolite SEP‐383103 was selected as the primary model based on prespecified criteria. Effect on ∆∆QTcF exceeding 10 ms can be excluded within observed ranges of ulotaront and SEP‐383103 plasma concentrations up to ~574 and ~272 ng/mL, respectively. The upper bound of 90% CI for ΔΔQTcF can be predicted to be below 10 ms at the highest anticipated clinical exposure, currently defined as steady‐state mean Cmax at ulotaront 100 mg/day in CYP2D6 poor metabolizers, ~416 and ~211 ng/mL for ulotaront and SEP‐383103, respectively. Assay sensitivity was demonstrated by the QTc effect caused by moxifloxacin. In conclusion, ulotaront is unlikely to cause clinically relevant QTc prolongation in patients with schizophrenia at the anticipated maximum therapeutic dose.