Extended Data Fig. 9. The binding details of XLIX with WDR6, and tissue distribution of XLIX, related to Fig. 7.
a, Molecular docking of WDR6 with indicated small molecule compounds. MOL009949 stands for XLIX. b, Left panel, chemical structure of XLIX. Right panel, molecular dynamics simulation of the interaction of WDR6 with XLIX. c, The predicted binding region of XLIX withWDR6. d,e, XLIX contents in serum (d) and liver (e) of 8-week-old C57BL/6J mice given XLIX (40 mg/kg/d, i.p.) or vehicle for 1 h. The concentrations were normalized to serum volume (mL) (d) and tissue weights (g) (e), respectively. f-i, Serum ALT (f), AST (g), BUN (h) and creatinine (i) levels of 4-week XLIX (40 mg/kg/d, i.p.) treated mice. j, Representative H&E staining of liver and kidney sections of mice indicated in (f-i). Scale bars, 50 μm. k-n, Serum TAG (k), FPG (l), insulin levels (m) and HOMA-IR index (n) of male mice after 3-week HFD feeding, followed by 4-week treatment with XLIX. o,p, IPGTT and IPITT of mice described in (k-n). q-t (♀), Serum TAG (q), FPG (r), insulin levels (s) and HOMA-IR index (t) of female mice described in (k-n). u, v (♀), IPGTT and IPITT of female mice described in (k-n). w (♀), Representative ORO staining of liver sections of female mice described in (k-n). Scale bars, 50 μm. x (♀), Liver TAG levels were measured in female mice described in (k-n), the concentrations were normalized to the protein content of the same sample. For (d-i), n = 5 biologically independent mice per group. (k-p), n = 6 biologically independent mice per group. (q-v), (x), n = 7 biologically independent mice per group. Data in (d)-(i), (k)-(v) and (x) are presented as mean ± SD, determined by unpaired two-sided Student’s t-test. * P < 0.05, ** P < 0.01, N.D. not detected.