| Identification | Back Directory | [Name]
GNE-6468 | [CAS]
1677668-27-7 | [Synonyms]
GNE-6468
Benzoic acid, 4-[6-(2-chloro-6-cyclopropylbenzoyl)imidazo[1,5-a]pyrimidin-8-yl]-2-hydroxy- | [Molecular Formula]
C23H16ClN3O4 | [MOL File]
1677668-27-7.mol | [Molecular Weight]
433.84 |
| Chemical Properties | Back Directory | [density ]
1.55±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 5 mg/mL (11.52 mM) | [form ]
Solid | [pka]
2.35±0.10(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
GNE-6468 is a potent and selective RORc inverse agonist. GNE-6468 displayed >300-fold selectivity for RORc over the other ROR family members, PPARγ, and NRs in our cellular selectivity panel. The favorable potency, selectivity, and physiochemical properties of GNE-6468, in addition to its potent suppression of IL-17 production in human primary cells, support its use as chemical biology tools to further explore the role of RORc in human biology. The nuclear receptor (NR) retinoic acid receptor-related orphan receptor gamma (RORγ, RORc, or NR1F3) is a promising target for the treatment of autoimmune diseases. RORc is a critical regulator in the production of the pro-inflammatory cytokine interleukin-17. | [Uses]
GNE-6468 is a highly potent and selective RORγ (RORc) inverse agonist with an EC50 value of 13 nM for HEK-293 cell. GNE-6468 exhibits an EC50 of 30 nM for IL-17 PBMC[1]. | [in vivo]
GNE-6468 (compound 28) displays high predicted clearance values in human and rodent hepatocytes (CLhep = 17 and 42 mL/min/kg, respectively) [1].
| [IC 50]
ROR-γ: 2 nM (EC50) | [References]
[1] Fauber BP, et al. Discovery of imidazo[1,5-a]pyridines and -pyrimidines as potent and selective RORc inverse agonists. Bioorg Med Chem Lett. 2015 Aug 1;25(15):2907-12. DOI:10.1016/j.bmcl.2015.05.055 |
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