GSK805 is a potent, orally bioavailable RORγγ Inhibitor, with pIC50 of 8.4 and >8.2 for RORγ FRET assay and Th17 assay. GSK805 suppresses T helper 17 (Th17) responses, including IL-17 and IFN-γ production (~ 500 nM). GSK805 directly and reversibly interacts with the ligand binding domain of RORγt to block its transcriptional effects. GSK805 induces RORγt binding to Gata3 resulting in increased expression of GATA3. GSK805 reduces the severity of autoimmune encephalomyelitis in murine models of multiple sclerosis (30 mg/kg/day, p.o.).
|Animal models||EAE mice|
|Dosages||once daily at 3 doses (1, 3, and 10 mg/kg)|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||DMSO 10 mM|
|Storage||-20°C, protect from light|
Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors.
Wang Y, et al. ACS Med Chem Lett. 2015 May 26;6(7):787-92. PMID: 26191367.
|Related ROR Products|
S18-000003 is a potent, effective and orally active inhibitor of retinoic acid receptor-related orphan receptor-gamma-t (RORγt), with an IC50 of 29 nM.
Neoruscogenin is a bioavailable, potent, and high-affinity agonist of the nuclear receptor RORα (NR1F1).
Vimirogant (also known as AGN-242428 and VTP-43742) is a potent, selective and orally active RORγt inhibitor.
SR2211 is a synthetic RORγ-selective modulator, functions as an inverse agonist, with a Ki of 105 nM and an IC50 of ~320 nM.
SR 1001 is a RORα/γ inverse agonist with Ki values of 172 and 111 nM, respectively.
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