General description
A cell-permeable pyrazolo compound that acts as a potent inhibitor against Akt (IC50 = 32, 17, and 47 nM against Akt1, Akt2, and Akt3, respectively), PKA (IC50 = 20 nM), and p70S6K (IC50 = 85 nM) in an ATP-competitive manner (Ki = 18 nM using AKT2), with much reduced activity toward RSK1 (IC50 >100 nM) and a panel of 13 other cellular kinases (IC50 >1 µM), including PDK1, PI 3-Kβ, SGK, GSK-3β, and MEK1. Shown to effectively reduce the phosphorylation levels of GSK-3β, S6R, and FKHRL1 (IC50 range from 2.08 to 4.45 µM against GSK-3β pSer9 level), as well as inhibit the proliferation (IC50 range from 0.94 to 11.86 µM) of cancer cells exhibiting constitutive Akt pathway activation, including the PTEN-deficient MES-SA uterine sarcoma and U87MG glioblastoma cell lines. AT7867 treatments via i.p. or p.o. (20 mg/kg and 90 mg/kg, respectively, once every 3 days) are also reported to result in Akt pathway and tumor growth inhibition in mice bearing MES-SA (~40% of untreated control on day 10 by i.p. or p.o.) or U87MG (~50% of untreated control on day 10 by i.p.) xenograft in vivo.
A cell-permeable pyrazolo compound that acts as a potent inhibitor against Akt (IC50 = 32, 17, and 47 nM against Akt1, Akt2, and Akt3, respectively), PKA (IC50 = 20 nM), and p70S6K (IC50 = 85 nM) in an ATP-competitive manner (Ki = 18 nM using AKT2), with much reduced potency toward RSK1 (IC50 >100 nM) and a panel of 13 other cellular kinases (IC50 >1 µM). Shown to reduce cellular phosphorylation of GSK-3β (IC50 range from 2.08 to 4.45 µM), S6R, FKHRL1, and inhibit the proliferation of cancer cells exhibiting constitutive Akt pathway activation both in vitro (IC50 range from 0.94 to 11.86 µM) and in mice in vivo (20 mg/kg via i.p. or 90 mg/kg via p.o.).
Packaging
Packaged under inert gas
Warning
Toxicity: Standard Handling (A)
Reconstitution
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Grimshaw, K.M., et al. 2010. Mol. Cancer Ther.9, 1100.
Saxty, G., et al. 2007. J. Med. Chem.50, 2293.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
- UPC:
- 12352200
- Condition:
- New
- Weight:
- 1.00 Ounces
- HazmatClass:
- No
- WeightUOM:
- LB
- MPN:
- 124033-10MG
