Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis.

ABSTRACT: Intrinsically disordered proteins (IDPs) are emerging as attractive drug targets by virtue of their prevalence in various diseases including cancer. Drug development targeting IDPs is challenging because they have dynamical structure features and conventional drug design is not applicable. NUPR1 is an IDP playing an important role in pancreatic cancer. We previously reported that Trifluoperazine (TFP), an antipsychotic agent, was capable of binding to NUPR1 and inhibiting tumors growth. Unfortunately, TFP showed strong central nervous system side-effects. In this work, we undertook a multidisciplinary approach to optimize TFP, based on the synergy of computer modeling, chemical synthesis, and a variety of biophysical, biochemical and biological evaluations. A family of TFP-derived compound

SUBMITTER: Santofimia-Castano P 

PROVIDER: S-EPMC6546470 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature