Identification of pimavanserin tartrate as a potent Ca²⁺-calcineurin-NFAT pathway inhibitor for glioblastoma therapy.

ABSTRACT: Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor, and 95% of patients die within 2 years after diagnosis. In this study, aiming to overcome chemoresistance to the first-line drug temozolomide (TMZ), we carried out research to discover a novel alternative drug targeting the oncogenic NFAT signaling pathway for GBM therapy. To accelerate the drug's clinical application, we took advantage of a drug repurposing strategy to identify novel NFAT signaling pathway inhibitors. After screening a set of 93 FDA-approved drugs with simple structures, we identified pimavanserin tartrate (PIM), an effective 5-HT_2A receptor inverse agonist used for the treatment of Parkinson's disease-associated psychiatric symptoms, as having the most potent inhibitory

SUBMITTER: Liu ZZ 

PROVIDER: S-EPMC8563877 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature