GDC0084 (RG7666) is a PI3K inhibitor with potential antineoplastic activity. GDC0084 (RG7666) specifically inhibits PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This may result in the inhibition of both cell growth and survival in susceptible tumor cell populations.

PI3Kγ:10 nM(Ki app), mTOR:70 nM(Ki app), PI3Kβ:46 nM(Ki app), PI3Kα:2 nM(Ki app), PI3Kδ:3 nM(Ki app)

In human microsomal and stem cell cultures, GDC-0084 showed good metabolic stability and inhibited pAKT, a key signal of the PI3K pathway, in normal brain tissues.GDC-0084 inhibited the proliferation of a variety of glioma cells (IC50: 0.3-1.1 μM).The binding rate of GDC-0084 to plasma proteins was low, and the free fraction of GDC-0084 in CD-1 mouse plasma was 29.5±2.0%. was 29.5±2.7% (n=3,5 μM), while the binding rate to brain tissue was higher in CD-1 mice with a free fraction of only 6.7±1% (n=3).

In human microsomal and stem cell cultures, GDC-0084 showed good metabolic stability and inhibited pAKT, a key signal of the PI3K pathway, in normal brain tissues.GDC-0084 inhibited the proliferation of a variety of glioma cells (IC50: 0.3-1.1 μM).The binding rate of GDC-0084 to plasma proteins was low, and the free fraction of GDC-0084 in CD-1 mouse plasma was 29.5±2.0%. was 29.5±2.7% (n=3,5 μM), while the binding rate to brain tissue was higher in CD-1 mice with a free fraction of only 6.7±1% (n=3).

For transport studies, cells are seeded on 24-well Millicell plates 4 days prior to use(polyethylene terephtalate membrane, 1 μm pore size) at a seeding density of 1.3×105 cells/ml). GDC-0084 is tested at 5 μM in the apical-tobasolateral (A-B) and basolateral-to-apical (B-A) directions. The compound is dissolved in transport buffer consisting of Hanks' balanced salt solution with 10 mM HEPES. Lucifer Yellow is used as the paracellular and monolayer integrity marker. GDC-0084 concentrations in the donor and receiving compartments are determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The apparent permeability (Papp), in the apical to A-B and B-A directions, is calculated after 2-hour incubation.(Only for Reference)

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 3.83 mg/mL (10.02 mM), Sonication is recommended.