Extended Data Fig. 9. AU-15330 is well tolerated in mice and induces on-target degradation of SMARCA2, SMARCA4, and PBRM1.
(a) Immunoblots of indicated proteins in B16F10 and MC38 cells treated with DMSO or AU-15330 (100 nM or 1 μM). Vinculin is the loading control probed on a representative immunoblot. This experiment was repeated independently twice. (b) Schematic outlining the AU-15330 in vivo study in non-tumor bearing CD-1 mice. Male mice were treated with vehicle (control) or AU-15330 at the indicated concentration throughout the experiment. (c) Pharmacokinetics profile of AU-15330 following intravenous (IV) injection in CD-1 mice. Mice received a single injection at indicated concentration of AU-15330, and plasma levels were determined by HPLC. Data are presented as mean +/− SD (n = 6, biological replicates). (d) Immunohistochemistry staining of SMARCA4/BRG1 was carried out using lung, small intestine, and prostate sections after necropsy to show on-target efficacy of AU-15330 in vivo (n = 2, biological replicates). (e) Body weight measurements showing AU-15330 does not affect weight of non-tumor bearing CD-1 mice. Data are presented as mean +/− SD (n = 6, biological replicates). (f) Major organ weight measurements (taken after necropsy) showing AU-15330 does not affect their weight in non-tumor bearing CD-1 mice. Data are presented as mean +/− SD (n = 6, biological replicates). (g) Complete blood count showing AU-15330 does not affect the hematologic system. Non-tumor bearing CD-1 mice were treated with vehicle or AU-15330 at the indicated concentration throughout the treatment period, and whole blood was then collected and processed. WBC, white blood cells; RBC, red blood cells; PLT, platelets. Data are presented as mean +/− SD (n = 6, biological replicates).