Velcrin molecular glues induce apoptosis in glioblastomas with high <i>PDE3A</i> and <i>SLFN12</i> expression.

ABSTRACT:

Background

Velcrins are molecular glues that kill cells by inducing the formation of a protein complex between the RNase SLFN12 and the phosphodiesterase PDE3A. Formation of the complex activates SLFN12, which cleaves tRNA^Leu(TAA) and induces apoptosis. Velcrins such as the clinical investigational compound, BAY 2666605, were found to have activity across multiple solid tumor cell lines from the cancer cell line encyclopedia, including glioblastoma cell lines. We therefore aim to characterize velcrins as novel therapeutic agents in glioblastoma.

Materials and methods

PDE3A and SLFN12 expression levels were measured in glioblastoma cell lines, the Cancer Genome Atlas (TCGA) tumor samples, and tumor neurospheres. Velcrin-treated cells were assayed for

SUBMITTER: Aquilanti E 

PROVIDER: S-EPMC11333922 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature