Fig. 2: Brain permeability of derivative 85, PU-HZ151, in mice and humans.
From: Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system
a Time-dependent molar concentration curve of PU-HZ151 in plasma and brain determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Non-CNS, metabolizing and non-metabolizing, organs as well as PU-H71 are shown for comparison. Probes were injected intravenously (i.v.) or by oral gavage (PO) at 10 mg kg−1 to healthy male B6D2F1 mice (n = 12 per experimental condition, 3 per time point). Data are presented as mean ± s.e.m. See also Supplementary Fig. 17. b Experimental design for positron emission tomography (PET) imaging in human patients. Images were obtained at 0.5, 3, and 24 h post [124I]-PU-HZ151 or [124I]-PU-H71 injection. non-CNS and non-Pgp organs and tissues are shown for reference. Graph, mean ± s.e.m. of n = 3 for [124I]-PU-HZ151 PET and n = 14 at 0.5 h; n = 24 at 3 h and 24 h for [124I]-PU-H71 PET. AUC area under the curve, SUV standard uptake value. c Representative axial brain PET images of normal (non-diseased) human brain obtained as in b at 0.5 and 24 h post [124I]-PU-HZ151 single injection. PU-HZ151 demonstrates penetration across BBB, with no binding to neurologic structures and complete washout by 24 h. [124I]-PU-H71 is shown for comparison. d A representative magnetic resonance imaging (MRI) overlaid with the PET image obtained at 3 h post [124I]-PU-HZ151 injection shows the anatomic localization of PU-HZ151. Scale bars, PET window display intensity scales, with upper and lower SUV thresholds. Source data are provided as a Source Data file.
