Dataset Information

Target deconvolution of SW016789 in human and mouse Beta cells

ABSTRACT: The target of SW016789 is unknown (PMCID: PMC9225822). This compound was identified in a high-throughput screen for insulin secretion modulators and was subsequently discovered to cause hypersecretory stress in beta cells. A photoaffinity probe was designed, Z629, based upon the structure of SW016789. Photo-crosslinking, click chemistry to biotin, and affinity purification with streptavidin-agarose was used to enrich for potential binding partners. Experiments were performed in both mouse MIN6 and human EndoC-BetaH1 beta cells. Enriched proteins were identified based on the ratio of PSMs detected in Z629 vs DMSO treatments. Candidate proteins (>2-fold) were filtered based on a >2-fold enrichment in Z629/DMSO and >1 PSM for Z629 in both MIN6 and EndoC-BetaH1. Pathway analysis indicated a role for the Vdac family of proteins which were previously identified to have an important role in Beta-cells during type 2 diabetes (PMCID: PMC6331340). Vdac1 was therefore chosen for validation studies.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Mus Musculus (ncbitaxon:10090)

SUBMITTER: Michael Kalwat Amber L. Mosley