SR0987 is a cell-permeable SR1078 analog with ~6-fold improved agonist potency toward T-cell-specific retinoic acid receptor-related orphan receptor ROR?t (EC50 ~800 nM in cell-based reporter assays) by targeting an allosteric pocket within the RORγt ligand-binding domain (LBD). In addition to upregulating RORγt target gene IL17A expression, SR0987 is shown to simultaneously downregulate surface immune checkpoint protein PD-1 expression by a yet unidentified mechanism among ex vivo differentiated murine TH17 cells, as well as PMA/ionophore-stimulated human Jurkat T cells and murine EL4 T lymphocytes.
SR0987 is a cell-permeable SR1078 analog with ~6-fold improved agonist potency.
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