Azasteroid Blockers of SULT2B1b Aim to Let T Cells Back Into Tumors
- SULT2B1b makes cholesterol sulfate, a metabolite that keeps T cells out of tumors and can blunt immune checkpoint therapy.
- A new azasteroid inhibitor series was identified, showing better potency and selectivity than earlier compounds against this enzyme.
- Co-crystal structures show the compounds sit in the active site differently from natural substrates, so they block the enzyme without being turned over.
- In mice, the inhibitors lowered cholesterol sulfate within tumors, supporting further study alongside checkpoint blockade.
💡 Points Based on the abstract
The non-substrate binding pose is the part I care about: it means the series is not just a steroid mimic that gets sulfonated, which should buy metabolic stability. But steroid-like scaffolds invite off-target worries against other SULTs and nuclear receptors, so I would want a broad selectivity panel and a look at tumor exposure before believing the immune story.
Small-Molecule Inhibitors of Cholesterol Sulfotransferase as Immunomodulatory Agents ↗