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. Author manuscript; available in PMC: 2019 Mar 28.
Published in final edited form as: Nature. 2018 Nov 7;563(7732):564–568. doi: 10.1038/s41586-018-0701-2

Fig. 3|. Development of an orally available, potent, small-molecule SPR inhibitor to limit BH4 production.

Fig. 3|

a, Chemical structure of SPRi3 and QM385. b, Dose-dependent reduction in plasma BH4 levels by QM385, and respective dose-dependent increase in plasma sepiapterin levels. BQL, below quantifiable limits (less than 0.3 ng ml–1 for sepiapterin). Data are shown as means ± s.e.m.; n = 6 mice for each condition. c, Left, representative histograms depicting three-day proliferation of stimulated CD4+ T cells with vehicle (n = 4 mice) and QM385 treatment (2.5 μM or 5 μM; n = 3 mice each); and right, quantitative analysis of total cell numbers. Data are shown as means ± s.e.m. The experiment was repeated two independent times with similar results. d, Top, diagram showing the HDM allergy model with dose-response administration of QM385 peritoneally twice a day for three consecutive days as indicated. Bottom, quantification of T cells and eosinophils in BALF. Data are shown as box-and-whisker plots (running from minimal to maximal values), for which individual data points are given. Vehicle, n = 10; 0.3 mg kg–1, n = 5; 1 mg kg–1, n = 4; 3 mg kg–1, n = 6/7. Absolute numbers in the BALF are shown. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001 (one-way ANOVA with Dunnett’s multiple comparisons for panels d, e).