New azasteroid SULT2B1b inhibitors lower tumor cholesterol sulfate
- Reports a new azasteroid class of inhibitors against SULT2B1b, the enzyme producing the immunosuppressive metabolite cholesterol sulfate.
- Compounds are described as more potent and more selective than earlier inhibitors, and engage the enzyme in a pose distinct from its natural substrates.
- In mouse tumors they lower cholesterol sulfate, and the authors propose pairing them with immune checkpoint blockade.
💡 Points Based on the abstract
A distinct binding pose versus the natural substrate is the interesting part: it suggests a route to selectivity over other SULTs, which steroid-like scaffolds usually struggle with. I'd want the SULT2A1/other-isoform panel and in vivo exposure before believing the immuno-oncology story. Does the checkpoint combination hold up beyond mouse models?
Small-Molecule Inhibitors of Cholesterol Sulfotransferase as Immunomodulatory Agents ↗