Figure 8
1G6-D7 inhibits expansion of pre-formed tumours in vivo. (A) A representative experiment showing tumour formation by injected parental MDA-MB-231 cells (5 × 106) over 35 days. On day 5 with an average tumour size of 60 mm3, either vehicle, control mouse IgG or 1G6-D7 was injected via IV (5 mg/kg) and around the tumour site (125 μg per injection). Measurement of the tumour volumes on live mice (n=4 or 5) was carried out every 5 days. This experiment was repeated twice. Data are represented as mean±s.e.m. P<0.05. (B) The images of the mice and the TV measurement of the excised tumours from the mice on day 36 (the s.d. represents three independent measurements with different angles of a tumour). (C) Based on the previously evaluated crystal structures of Hsp90α’s NTD (green) and MD (blue) plus CTD (red) domains and their fit into a cryoEM map of full-length Hsp90α bound to Hop (MODELLERv9.14). Lysine-270 and lysine-277 are located in the unstructured linker region (LR) between the NTD and MD domains, called F-5. Inhibitors, such as 1G6-D7, targeting the dual lysine residues (larger box) could block secreted Hsp90α-triggered tumourigenesis.
