A-674563 HCl

2 years -80 in solvent

A-674563 is administered 30 minutes before the 1 g/kg glucose challenge.

MiaPaCa-2 cells

20 or 100 mg/kg

11 nM (Ki), 11 nM (Ki), 11 nM (Ki), 11 nM (Ki), 11 nM (Ki), 11 nM (Ki)

20 mg/kg A-674563 increases plasma insulin in an oral glucose tolerance test. A-674563 shows no significant monotherapy tumor inhibitory activity, the efficacy of the combination therapy is significantly improved compared to paclitaxel monotherapy. [1] A674563-treated (20 mg/kg/bid, p.o.) mice exhibits slower tumor growth and more than 50% decrease in the tumor volume at the termination of the study compared with that in control group. [2] A-674563 is identified to have drastically improved PK profile with oral bioavailability of 67% in mouse, but is 70-fold less active than A-443654. [3]

Akt Kinase Assay, The kinase assay uses His-Akt1 and a biotinylated mouse Bad peptide as substrate. The kinase assay is carried out at room temperature for 30 minutes in 50 uL of reaction buffer [20 mM HEPES, pH 7.5, 10 mM MgCl2, 0.1% (w/v) Triton X-100, 5 uM ATP (Km = 40 uM), 5 uM peptide (Km = 15 uM), 1 mM DTT, 60 ng of Akt1, and 0.5 uCi of [gamma-33P]ATP] in the presence of different concentrations of A-674563. Each reaction is stopped by adding 50 uL of termination buffer (0.1 M EDTA, pH 8.0, and 4 M NaCl). The biotinylated Bad peptides are immobilized on streptavidin-coated FLASH plates. After being washed with PBS-Tween 20 (0.05%), the 33P phosphopeptide captured on the FLASH plates is measured with a TopCount Packard Instruments gamma counter.

DMSO 72 mg/mL, Water 72 mg/mL, Ethanol 18 mg/mL

(2S)-1-(5-(3-methyl-1H-indazol-5-yl)pyridin-3-yloxy)-3-phenylpropan-2-amine