Subasumstat

Subasumstat (CAS No.: 1858276-04-6) is a class of synthetic small-molecule chemical biology tools and lead-like probes, classified as a first-in-class modulator of the SUMOylation enzyme cascade pathway, primarily serving basic and early-discovery research in immuno-oncology and protein post-translational modification; by selectively targeting the SUMO-activating enzyme E1 heterodimer (SAE1/UBA2), it forms a covalent adduct with SUMO at the E1 active site, thereby blocking the transfer of SUMO to the E2 conjugating enzyme UBC9, inhibiting global protein SUMOylation and perturbing SUMO-dependent signaling networks, including key programs involved in transcriptional regulation, DNA damage response, and cell cycle control. Consistent with the above pathway intervention, this molecule can induce type I interferon-related gene expression profiles and promote phosphorylation of STAT1 and STAT2 in cellular systems, while enhancing macrophage phagocytic function and natural killer cell-mediated cytotoxicity; in in vitro evaluations, it exhibits nanomolar-level highly selective inhibitory activity against the E1 complex, and its cellular-level effects are typically in the nanomolar to low micromolar range, influenced by factors such as cellular background, experimental format, and exposure time. In mouse tumor-related models, biomarkers of pathway engagement can be detected, such as an overall decrease in SUMO-conjugated protein levels in tumor tissue accompanied by upregulation of interferon-regulated genes. As a research reagent, Subasumstat is commonly used for systematic analysis of the crosstalk between SUMOylation biology and innate immune pathways, and for oncology-focused combination strategies and mechanistic screening; typical applications cover multiple experimental platforms, including human and mouse cell lines, primary immune cell systems, and syngeneic or xenograft models, with the specific concentrations or doses used in experiments generally determined by the research objective and experimental design.