PI3K/mTOR Dual Inhibitor Pictilisib Stably Binds to Site I of Human Serum Albumin as Observed by Computer Simulation, Multispectroscopic, and Microscopic Studies.

ABSTRACT: Pictilisib (GDC-0941) is a well-known dual inhibitor of class I PI3K and mTOR and is presently undergoing phase 2 clinical trials for cancer treatment. The present work investigated the dynamic behaviors and interaction mechanism between GDC-0941 and human serum albumin (HSA). Molecular docking and MD trajectory analyses revealed that GDC-0941 bound to HSA and that the binding site was positioned in subdomain IIA at Sudlow's site I of HSA. The fluorescence intensity of HSA was strongly quenched by GDC-0941, and results showed that the HSA-GDC-0941 interaction was a static process caused by ground-state complex formation. The association constant of the HSA-GDC-0941 complex was approximately 10⁵ M^-1, reflecting moderate affinity. Thermodynamic analysis conclusions were

SUBMITTER: Yang H 

PROVIDER: S-EPMC9413508 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature