Poster Presentation The 46th Lorne Conference on Protein Structure and Function 2021

Identification and validation of new chemical scaffolds for Hsp90 (#208)

Eva Antony 1 , Raina Chand 1 , Ivanhoe Leung 1 , Johannes Reynisson 1
  1. University of Auckland, Auckland, NOT US OR CANADA, New Zealand

Oncogenic proteins in tumour cells rely on molecular chaperones such as Hsp90 for their proper folding and maturation1. Hsp90 is therefore a potential inhibition target for the development of new anticancer agents. The chaperoning activity of Hsp90 is regulated by ATP hydrolysis. ATP binds at the N-terminal domain of Hsp90. Herein, we report our work using virtual high-throughput screening and biophysical techniques in the identification and validation of new chemical scaffolds that binds the N-domain of Hsp902. Our work may provide insights into the development of new Hsp90 N-domain inhibitors.

References:

1. Mielczarek-Lewandowska A, Hartman ML, Czyz M. Inhibitors of HSP90 in melanoma. Apoptosis. 2020;25(1-2):12-28. doi:10.1007/s10495-019-01577-1

2. Huang R, Ayine-Tora DM, Muhammad Rosdi MN, Li Y, Reynisson J, Leung IKH. Virtual screening and biophysical studies lead to HSP90 inhibitors. Bioorganic Med Chem Lett. 2017;27(2):277-       281. doi:10.1016/j.bmcl.2016.11.059