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Utreloxastat (PTC857) is a 15‐lipoxygenase inhibitor being developed to treat amyotrophic lateral sclerosis. This first‐in‐human study investigated the safety and pharmacokinetics of utreloxastat in healthy volunteers (N = 82) in a double‐blind, placebo‐controlled trial. The effects of a single ascending dose (100–1000 mg), multiple ascending doses (150–500 mg), and food (500 mg) on the pharmacokinetics and safety of utreloxastat were evaluated. Following single doses, the time to maximum plasma concentration (Cmax) was observed ≈4 hours after dosing and the terminal half‐life ranged from 20 to 25.3 hours. The Cmaxand area under the concentration‐time curve (AUC) increased slightly over dose proportionally. Following multiple doses (once daily/twice daily), the apparent clearance reduced and terminal half‐life was ≥33 hours. There was no apparent difference of exposure following morning or evening doses. Varying diets increased the Cmaxand AUCs of utreloxastat but did not alter time to Cmax. There were no gender‐based differences in exposure. Utreloxastat showed no marked safety signal following single doses up to 1000 mg and multiple doses over 14 days of 500 mg once daily or 250 mg twice daily. The results support further development of utreloxastat for the treatment of patients with amyotrophic lateral sclerosis at a 250‐mg twice‐daily dose administered with food.

Mass spectrometry-based tissue profiling and imaging are technologies that allow identification and visualization of protein signals directly on thin sections cut from fresh frozen tissue specimens. These technologies were utilized to evaluate protein expression profiles in the normal mouse prostate during development (1–5 weeks of age), at sexual maturation (6 weeks of age), and in adult prostate (at 10, 15, or 40 weeks of age). The evolution of protein expression during normal prostate development and maturation were subsequently compared with 15-week prostate tumors derived from genetically engineered mice carrying the Large T antigen gene under regulation of the prostate-specific probasin promoter (LPB-Tag mouse model for prostate cancer). This approach identified proteins differentially expressed at specific time points during prostate development. Furthermore expression of some of these proteins, for example probasin and spermine-binding protein, were associated with prostate maturation, and prostate tumor formation resulted in their loss of expression. Cyclophilin A, a protein found in other cancers, was differentially -acetylated on the N terminus, and both isoforms appeared during normal prostate and prostate tumor development. Imaging mass spectrometry localized the protein signals to specific prostatic lobes or regions. Thus, tissue profiling and imaging can be utilized to analyze the ontogeny of protein expression during prostate morphogenesis and tumorigenesis and identify proteins that could potentially serve as biomarkers for prostate cancer.

Mass spectrometry-based tissue profiling and imaging are technologies that allow identification and visualization of protein signals directly on thin sections cut from fresh frozen tissue specimens. These technologies were utilized to evaluate protein expression profiles in the normal mouse prostate during development (1–5 weeks of age), at sexual maturation (6 weeks of age), and in adult prostate (at 10, 15, or 40 weeks of age). The evolution of protein expression during normal prostate development and maturation were subsequently compared with 15-week prostate tumors derived from genetically engineered mice carrying the Large T antigen gene under regulation of the prostate-specific probasin promoter (LPB-Tag mouse model for prostate cancer). This approach identified proteins differentially expressed at specific time points during prostate development. Furthermore expression of some of these proteins, for example probasin and spermine-binding protein, were associated with prostate maturation, and prostate tumor formation resulted in their loss of expression. Cyclophilin A, a protein found in other cancers, was differentially α-acetylated on the N terminus, and both isoforms appeared during normal prostate and prostate tumor development. Imaging mass spectrometry localized the protein signals to specific prostatic lobes or regions. Thus, tissue profiling and imaging can be utilized to analyze the ontogeny of protein expression during prostate morphogenesis and tumorigenesis and identify proteins that could potentially serve as biomarkers for prostate cancer.

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