GSK2245035 (C09-1135-959)

GSK2245035 is a highly potent and selective intranasal Toll-Like receptor 7 (TLR7) agonist with preferential Type-1 interferon (IFN)-stimulating properties. GSK2245035 has pEC 50 s of 9.3 and 6.5 for IFNα and TFNα. GSK2245035 effectively suppresses allergen-induced Th2 cytokine production in human peripheral blood cell cultures. GSK2245035 is used for asthmaIn VitroGSK2245035 (0.01, 0.1, 1, 10, 100, 1000, 10000 nM; 6 days) reduces levels of the Th2 cytokines IL-5 and IL-13 released in response to Timothy grass or house dust mite in human PBMC cultures derived from individuals allergic to these allergens, in a dose-dependent manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoGSK2245035 (i.n.; 0.03-1 mg/kg; 6 hours) makes dose-related increasing in IFNα levels in serum at doses of 0.3 mg/kg and above at the 2 h time point which had subsided at 6 h . GSK2245035 (3, 30, 300, 3000 ng/kg; 6 hours) treatment can make plasma IP-10 provided the most sensitive biomarker of target engagement with raised levels of this chemokine detected at doses of 30 ng/kg and above in the cynomolgus monkey . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female BALB/c mice Dosage: 0.03, 0.1, 0.3, 1 mg/kg Administration: Intranasally (i.n.); 6 hours Result: Dose-related increases in IFNα levels in serum were detected at doses of 0.3 mg/kg and above at the 2 h time point which had subsided at 6 h.IC50& Target:TLR7 IFNα 9.3 (pEC 50 ) CD40 6.5 (pEC 50 ). Specifications and Purity: 10mM in DMSO. Molecular Formula: C20H34N6O2. Molecular Weight: 390.52.