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Related Articles from SNS

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

Abstract BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1,2,3.

Nature 19h ago

SpliceBind: Isoform-Aware Prediction of Binding Pocket Druggability

arXiv:2606.04020v1 Announce Type: cross Abstract: Splice-mediated drug resistance occurs in up to 40% of patients on targeted kinase inhibitors, yet state-of-the-art druggability tools operate on single structures and cannot compare across isoforms. We introduce SpliceBind, a graph neural network framework for isoform-aware druggability prediction. Beyond improving prediction accuracy (AUROC 0.703 vs. P2Rank 0.634, p = 0.026), we address a more fundamental question: when do structural...

arXiv CS 6d ago

Structural basis for chaperone-guided assembly of RNA-induced silencing complex

Abstract The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process1,2,3, but the molecular mechanism remains poorly understood. Here we identify the human AGO–HSP90–p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC).

Nature 19h ago