| Description | GSK805 is a potent, orally bioavailable retinoid-related orphan receptor gamma t (RORγt) inverse agonist that interacts with the receptor's putative ligand binding domain without exerting significant effects on DNA binding |
| In vitro | GSK805 inhibits the expression of IL-17 (at 0.5 μM) in na?ve CD4+ T cells activated under Th17-cell-polarizing conditions and affects the broader RORγt-dependent gene network, inhibiting the development and pathogenic function of Th17 cells[1]. |
| In vivo | GSK805 significantly reduces the severity of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, when given orally to the hosts at 10 mg/kg daily beginning at the time of disease induction[1]. |
| Cell experiments | CD4+CD62LhighCD25? naive CD4+ T cells were purified by FACS sorting following a MACS bead isolation of CD4+ cells. Naive CD4+ cells were activated with plate-bound anti-CD3 (2 μg/ml) and anti-CD28 (2 μg/ml). For Th17 cell differentiation, cultures were supplemented with IL-6 (20 ng/ml) plus TGF-β1 (1 ng/ml), and IL-23 (10 ng/ml) was added after 48 h. RORγt inhibitors or vehicle control DMSO was also included in the cultures. After 96 h, cells were collected for further experiments[1]. |
| molecular weight | 532.36 |
| Molecular formula | C23H18Cl2F3NO4S |
| CAS | 1426802-50-7 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 100 mg/mL (187.84 mM) |
| References | 1. Xiao S , Yosef N , Yang J , et al. Small-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms[J]. Immunity, 2014, 40(4):477-489. 2. Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors[J]. ACS Medicinal Chemistry Letters:-. |