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PI4KIII beta inhibitor 3

CAS No. : 1245319-54-3

MCE 国际站：PI4KIII beta inhibitor 3

产品活性：PI4KIII beta inhibitor 3 是一种新型高效的 ΡΙ4ΚΙΙΙβ 抑制剂，IC₅₀ 为 5.7 nM。

研究领域：PI3K/Akt/mTOR

作用靶点：PI4K

In Vitro: PI4KIII beta inhibitor 3 is a PI4KIII inhibitor extracted from patent WO/2013034738 A1, the compound of formula 3, has an IC₅₀ of 5.7 nM. PI4KIII beta inhibitor 3 exerts significant immunosuppressive activity, with IC₅₀ value of 3 nM in the mixed lymphocyte reaction (MLR) assay. PI4KIII beta inhibitor 3 inhibits IL2 and IFNy secretion with IC₅₀ values of less than InM in each case. Thus, PI4KIII beta inhibitor 3 is shown to be as effective at inhibiting IL2 and IFNy secretion as conventional immunosuppressants such as cyclosporine A. IC₅₀ on IFNy and IL-2 release of Cyclosporine A are 2nM and less than 1 nM respectively.

In Vivo: PI4KIII beta inhibitor 3 (40 mg/kg per day, n=12) is able to delay the onset of arthritic symptoms and also to decrease symptom severity in a preventive model of arthritis compared to a vehicle control (MC 1%, n=12). PI4KIII beta inhibitor 3 reduces the anti-CII IgG titre and histological scores in the collagen-induced arthritis mouse model. Oral administration of PI4KIII beta inhibitor 3 results in prolonged graft survival in 3 out of 6 grafts in each group at day 30. Several grafts continued beating after withdrawal of the treatment (up to 60 days), indicating the induction of a certain type of graft tolerance. To evaluate the operational tolerance phenotype, animals with functional graft at day 60 are challenged with a second graft from the same donor strain or from a third party. No treatment is applied. The second grafts from the third party are rejected at day 8 (n=2) whereas second grafts from the same donor strain are functional for more than 90 days (n=2).

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