CAY10505

Administered via p.o.

Bone marrow cells

ca.10 mM

0.6 mg/kg

CAY10505 selectively inhibits PI3Kgamma isoform, with an IC50 of 30 nM better than the PI3Kalpha, beta, and delta isoforms, with IC50 of 0.94, 20 and 20 uM, respectively. Tested against a panel of 80 other kinases including casein kinase 2, CAY10505 significantly inhibits only the unrelated casein kinase 2 (CK20) with an IC50 of 20 nM. CAY10505 also inhibits the phosphorylation of the PI3K substrate PKB/Akt in mouse macrophages with an IC50 of 228 nM. CAY10505 inhibits C5a-mediated PKB/Akt phosphorylation in Raw-264 macrophages, with an IC50 of 0.23 nM. In human monocytic cell line THP-1, MCP-1, binding to the GPCR chemokine receptor CCR2, strongly induces phosphorylation of PKB/Akt, which is effectively inhibited by 26 at IC50 values as low as 0.4 uM. CAY10505 inhibits MCP-1-mediated chemotaxis in wild-type primary monocytes in a concentration-dependent manner with an IC50 of 52 uM, as well as in the monocytic cell line THP-1 with an IC50 of 53 uM. [1]

3 hours

Bone marrow cells are isolated, prepared, and stimulated. For in vitro chemotaxis, 107 5-day-derived BMDMs are suspended in 1 mL of medium containing 0.5% BSA and CAY10505 or DMSO and applied to the upper chamber of a transwell, 5 um pore size, chemotaxis plate. An amount of 600 uL of medium containing MCP-1/CCL2 and inhibitors or DMSO is added to the lower chamber. After 3 hours of incubation at 37 C and 5% CO2, the number of cells in the lower chamber is quantified with a Coulter.

CAY10505 Chemical Structure

DMSO 58 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL