Complex Crystal Structure Determination and in vitro Anti-non-small Cell Lung Cancer Activity of Hsp90 ^N Inhibitor SNX-2112.

ABSTRACT: SNX-2112, as a promising anticancer lead compound targeting heat shock protein 90 (Hsp90), absence of complex crystal structure of Hsp90 ^N -SNX-2112 hindered further structural optimization and understanding on molecular interaction mechanism. Herein, a high-resolution complex crystal structure of Hsp90 ^N -SNX-2112 was successfully determined by X-ray diffraction, resolution limit, 2.14 Å, PDB ID 6LTK, and their molecular interaction was analyzed in detail, which suggested that SNX-2112 was well accommodated in the ATP-binding pocket to disable molecular chaperone activity of Hsp90, therefore exhibiting favorable inhibiting activity on three non-small cell lung cancer (NSCLC) cell lines (IC₅₀, 0.50 ± 0.01 μM for A549, 1.14 ± 1.11 μM for H1299,

SUBMITTER: Zhao D 

PROVIDER: S-EPMC8039390 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature