CCT128930 hydrochloride是一种有效且选择性的 AKT 抑制剂 (IC₅₀=6 nM)。CCT128930 hydrochloride 通过靶向 AKT 的 Met282 (PKA-AKT 嵌合体的 Met173)，对 PKA 激酶 (IC₅₀=168 nM) 具有 28 倍的选择性，对 p70S6K (IC₅₀=120 nM) 具有 20 倍的选择性。具有抗肿瘤活性。

CCT128930 hydrochloride is a potent and selective inhibitor of AKT (IC 50 =6 nM). CCT128930 hydrochloride has 28-fold selectivity over the closely related PKA kinase (IC 50 =168 nM) through the targeting of Met282 of AKT (Met173 of PKA-AKT chimera), as well as 20-fold selectivity over p70S6K (IC 50 =120 nM). CCT128930 hydrochloride induces cell cycle arrest, DNA damage, and autophagy. Antitumor activity.

Solid

Akt2 6 nM (IC50) PKA 168 nM (IC50u

The GI50 values of CCT128930 hydrochloride for growth inhibition are 6.3 μM for U87MG human glioblastoma cells, 0.35 μM for LNCaP human prostate cancer cells, and 1.9 μM for PC3 human prostate cancer cells, all of which are PTEN-deficient human tumor cell lines.
CCT128930 (0.1-60 μM; 1 hour; U87MG human glioblastoma cells) hydrochloride shows an initial induction of AKT phosphorylation at serine 473 up to 20 μM, followed by a decreased in phosphorylation at higher concentrations.
CCT128930 hydrochloride inhibits direct substrates of AKT (Ser9 GSK3β, pThr246 PRAS40 and pT24 FOXO1/p32 FOXO3a) at ≥5 μM, and the downstream target, pSer235/236 S6RP at ≥10 μM, with generally constant levels of the respective total proteins and GAPDH.
CCT128930 (18.9 μM; U87MG human glioblastoma cells) hydrochloride causes an increase in phosphorylation of pSer473 AKT after 30

CCT128930 (25 or 40 mg/kg; i.p. daily or twice daily for 5 days) hydrochloride shows antitumor activities in U87MG and BT474 human breast cancer xenografts. Summary of the pharmacokinetic parameters of CCT128930 (25 mg/kg) in CrTacNCr-Fox1nu mice
Tissue Route

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. Yap TA et al. Preclinical pharmacology, antitumor activity, and development of pharmacodynamic markers for the novel, potent AKT inhibitor CCT128930. Mol Cancer Ther. 2011 Feb;10(2):360-71.
[2]. Wang FZ, et al. CCT128930 induces cell cycle arrest, DNA damage, and autophagy independent of Akt inhibition. Biochimie. 2014;103:118-125.

In Vitro: DMSO : 20 mg/mL (52.87 mM; ultrasonic and warming and heat to 60°C)配制储备液