Inhibitor of PI3Kγ
CAY10505 is a potent and selective PI3Kγ inhibitor (IC50= 30 nM)
PI3K (phosphatidylinositol-4,5-bisphosphate 3-kinase) is a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. It plays a key role in PI3K/Akt/mTOR pathway.
In neurons treated with 3.5 μM BA, 200 nM CAY10505 partially reduced the baicalein-induced Akt phosphorylation. [1]
In hypertensive rats, CAY10505 at 0.6 mg.kg-1 p.o. exhibited the following effects 1) effectively reduced MABP; 2) significantly ameliorated vascular endothelium dysfunction in hypertensive rats in combination of DOCA; 3) prominently increased serum nitrite and/or nitrate concentrations.4) prevented hypertension-induced attenuation of ACh-induced endothelium-dependent relaxation.[2]
参考文献:
[1] Tyagi S, Sharma S, Budhiraja RD.? Effect of phosphatidylinositol 3-kinase-γ inhibitor CAY10505 in hypertension, and its associated vascular endothelium dysfunction in rats.? Can J Physiol Pharmacol. 2012 Jul;90(7):881-5.
[2] Sun YY, Lin SH, Lin HC et al.? Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes. PLoS One.? 2013 Jul 19;8(7):e69019.
Cell experiment: | Up to 5×104 multiple myeloma (MM) cells/100 μL of medium per well are seeded in 96-well-plates. Primary MM cells are always seeded into wells containing primary bone marrow stromal cells. Drugs (e.g., CAY10505) are dissolved in either DMSO or acidified ethanol (in the case of melphalan) and kept as frozen stock solutions of 10-50 mM. Working dilutions in fullmedium are always freshly prepared. In the case of Bortezomib small volumes of single-thaw stock solution aliquots are prepared. Drug dilutions (e.g., CAY10505, 2.5, 5, 7.5 and 10 μM) are added to MM cells as 100 μL of 2× the final concentration per well for single-drug treatments, and in appropriate volumes of higher concentrations for drug combinations. Solvent controls are always included[2]. |
Animal experiment: | Rats[3]Wistar albino rats (180-240 g) of either sex are employed in the present study. For each group, the number of rats used (n) is 6. Group I (normal control): Rats are maintained on a diet of normal chow with drinking water. Group II (hypertensive control): Rats are unilaterally nephrectomized (uninephrectomised) and DOCA (40 mg/kg) is administered by subcutaneous injection (s.c.) twice weekly for 6 weeks, and then the untreated drinking water is replaced with a 1% NaCl solution. Group III (hypertensive rats): Rats are treated with CAY10505 (0.6 mg/kg, per os (p.o)) for 1 week after 5 weeks of treatment with DOCA. Group IV (hypertensive rats): Rats are treated with Losartan (25 mg/kg, p.o.) for 1 week after 5 weeks of treatment with DOCA. Group V (hypertensive rats): Rats are treated with Atorvastatin (30 mg/kg, p.o.) for 1 week after 5 weeks of treatment with DOCA. |
参考文献: [1]. Sun YY, Lin SH et al. Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes. 2013 Jul 19;8(7):e69019. | |
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