High-Throughput Targeted Drug Screening for NF1-associated High-Grade Gliomas with ATRX Deficiency.

ABSTRACT: Neurofibromatosis type 1 (NF1)-associated high-grade gliomas (HGGs) harboring ATRX mutations exhibit an aggressive clinical phenotype, driven by heightened genomic instability and metabolic reprogramming. Existing therapies, including chemotherapy and radiotherapy, are limited by resistance mechanisms and formation of secondary malignancy, underscoring the need for novel therapeutic strategies. Here, we report the results of a high-throughput screening of 10,000 small molecules aimed at identifying compounds selectively targeting vulnerabilities associated with concurrent ATRX and NF1 loss. Among the screened compounds, K784-6195 (ChemDiv ID) emerged as a promising candidate, exhibiting marked selective cytotoxicity in NF1-associated glioma cell lines with ATRX deficiency (IC50 = 4.84 μM).

SUBMITTER: Dubey S 

PROVIDER: S-EPMC12258913 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature