Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex

DE Bussiere, L Xie, H Srinivas, W Shu, A Burke… - Nature Chemical …, 2020 - nature.com
The anticancer agent indisulam inhibits cell proliferation by causing degradation of RBM39,
an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and …

Structural basis and kinetic pathway of RBM39 recruitment to DCAF15 by a sulfonamide molecular glue E7820

X Du, OA Volkov, RM Czerwinski, HL Tan, C Huerta… - Structure, 2019 - cell.com
E7820 and indisulam are two examples of aryl sulfonamides that recruit RBM39 to Rbx-Cul4-
DDA1-DDB1-DCAF15 E3 ligase complex, leading to its ubiquitination and degradation by …

Aryl sulfonamides degrade RBM39 and RBM23 by recruitment to CRL4-DCAF15

TC Ting, M Goralski, K Klein, B Wang, J Kim, Y Xie… - Cell Reports, 2019 - cell.com
Indisulam and related sulfonamides recruit the splicing factor RBM39 to the CRL4-DCAF15
E3 ubiquitin ligase, resulting in RBM39 ubiquitination and degradation. Here, we used a …

Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15

TB Faust, H Yoon, RP Nowak, KA Donovan, Z Li… - Nature chemical …, 2020 - nature.com
The investigational drugs E7820, indisulam and tasisulam (aryl-sulfonamides) promote the
degradation of the splicing factor RBM39 in a proteasome-dependent mechanism. While the …

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

T Han, M Goralski, N Gaskill, E Capota, J Kim, TC Ting… - Science, 2017 - science.org
INTRODUCTION Indisulam is an aryl sulfonamide drug that inhibits the proliferation of
certain human cancer cell lines. Its mechanism of action and the mechanism underlying its …

[HTML][HTML] Template-assisted covalent modification of DCAF16 underlies activity of BRD4 molecular glue degraders

YD Li, MW Ma, MM Hassan, M Hunkeler, M Teng… - BioRxiv, 2023 - ncbi.nlm.nih.gov
Small molecules that induce protein-protein interactions to exert proximity-driven
pharmacology such as targeted protein degradation are a powerful class of therapeutics 1 …

CRISPR screen reveals BRD2/4 molecular glue-like degrader via recruitment of DCAF16

AG Shergalis, VL Marin, DY Rhee… - ACS chemical …, 2023 - ACS Publications
Molecular glues (MGs) are monovalent small molecules that induce an interaction between
proteins (native or non-native partners) by altering the protein–protein interaction (PPI) …

Targeting the spliceosome through RBM39 degradation results in exceptional responses in high-risk neuroblastoma models

S Singh, W Quarni, M Goralski, S Wan, H Jin… - Science …, 2021 - science.org
Aberrant alternative pre-mRNA splicing plays a critical role in MYC-driven cancers and
therefore may represent a therapeutic vulnerability. Here, we show that neuroblastoma, a …

RNA‐binding motif protein 39 (RBM39): an emerging cancer target

Y Xu, A Nijhuis, HC Keun - British journal of pharmacology, 2022 - Wiley Online Library
RNA‐binding motif protein 39 (RBM39) is an RNA‐binding protein involved in transcriptional
co‐regulation and alternative RNA splicing. Recent studies have revealed that RBM39 is the …

Dual targeting of DDX3 and eIF4A by the translation inhibitor rocaglamide A

M Chen, M Asanuma, M Takahashi, Y Shichino… - Cell chemical …, 2021 - cell.com
The translation inhibitor rocaglamide A (RocA) has shown promising antitumor activity
because it uniquely clamps eukaryotic initiation factor (eIF) 4A onto polypurine RNA for …