Fig. 1: The oral ABCG2 inhibitor K31 prevents phototoxicity in an EPP mouse model.
From: Inhibition of ABCG2 prevents phototoxicity in a mouse model of erythropoietic protoporphyria
a The development of K31 through the structural modification of Ko143. b The inhibitory activity of K31 and Ko143 on ABCG2 (n = 4 for each concentration). Data are expressed as mean ± SEM. c Metabolic stability of Ko143 and K31 in incubations (n = 3 for each time point) with human liver microsomes. Data are expressed as mean ± SEM. ****P < 0.0001, two-way ANOVA with Šidák’s multiple comparisons test. d Pharmacokinetics of Ko143 and K31 in WT mice. Blood samples (n = 4 for each time point) were collected from the mice treated with Ko143 or K31 (100 mg/kg, po). Ko143 and K31 in sera were analyzed by UPLC-QTOFMS. The inset panel shows the areas under the curve (AUC) of Ko143 and K31. Data are expressed as median with range. *P = 0.0286, two-tailed Mann–Whitney test. e, f The effects of K31 on phototoxicity in Fech-mut mice (male). The back skin of Fech-mut mice was shaved, and they were then treated with K31 (100 mg/kg, po, once daily for 5 days). Forty min after K31 treatment, these mice were exposed to light for 20 min. e Gross appearance of the skin in Fech-mut mice pretreated with K31. f The ratio of injured areas vs shaved areas of skin. Data are expressed as mean ± SEM (n = 6 mice). ****P < 0.0001, one-way ANOVA with Dunnett’s multiple comparisons test. N.D. not detected. Source data are provided as a Source Data file.
