Fig. 1. Indisulam is highly efficacious in in vitro models of neuroblastoma.

a Aryl sulfonamides such as indisulam (red) act as a molecular glue bringing together DCAF15 E3 ubiquitin ligase and RNA binding protein RBM39 resulting in poly-ubiquitination and degradation of the protein. Depletion of RBM39 leads to aberrant splicing defects. b. Median indisulam area-under-curve (AUC) in cell lines from 26 tumour origins. Data was acquired from the CTD² network²⁴, each circle represents one cell line. c Indisulam AUC of 14 neural-crest derived neuroblastoma (NB) compared to non-NB cell lines (all other cancer lineages, n = 744 cell lines). Each circle represents one cell line. Data were acquired from the CTD² network²⁴ d Neuroblastoma lines IMR-32 and KELLY were treated with a 5-point dose-response of indisulam or vehicle control (VC, 0.1% DMSO) for 72 h. Cell growth determined by SRB assay (n = 3 independent experiments). e IMR-32 and KELLY cells were grown in 3D spheroids and treated with indisulam or VC (0.1% DMSO) for 72 h. ATP was measured with Cell-Titre-Glo 3D. (IMR-32 n = 3 independent experiments, KELLY n = 2 independent experiments). f Overview of workflow of proteomic and RNAseq analysis in IMR-32. Data are represented as mean values ± SD. d, e Statistical significance in c was determined by a Mann Whitney test. Source data is provided as a Source Data File.