CZC24832 is a selective inhibitor of PI 3-kinase γ.

PI3Kδ:8.194 μM, PI3Kβ:1.1 μM, PI3Kγ:27 nM

In a therapeutic model of collagen-induced arthritis (CIA), mice administered 10 mg/kg of CZC24832 orally twice daily exhibited significant reductions in both bone and cartilage destruction and overall clinical parameters. Additionally, in an IL-8-dependent air-pouch model, CZC24832 demonstrated a dose-dependent decrease in granulocyte recruitment, consistent with the level of inhibition observed in mice lacking PI3Kγ.

In the BT system, treatment with CZC24832 significantly inhibits IL-17A (IC50 = 1.5 μM) as well as B-cell activation markers, such as IL-6 and IgG. Moreover, in T-cell systems, such as in human umbilical vein endothelial cells, the production of IL17A is strongly suppressed, indicating that PI3Kγ kinase activity plays a broad role in the functionality of TH17 cells. Accordingly, CZC24832 inhibits the differentiation of TH17 cells. A high-throughput screening of 154 lipid and protein kinases, alongside 922 other proteins, identified only PI3Kβ and PIP4K2C as off-target proteins within a 100-fold selectivity window.

AZD4547 kinase activity: The ability of AZD4547 to inhibit the human recombinant kinase activities of FGFR1-3 is tested using ATP concentrations at, or just below, the respective Km.