Ipatasertib dihydrochloride (GDC-0068 dihydrochloride) 是一种选择性的，ATP竞争性的 pan-Akt 抑制剂，抑制 Akt1，Akt2，Akt3 的 IC₅₀ 分别为 5，18，8 nM。

Ipatasertib dihydrochloride (GDC-0068 dihydrochloride) is a highly selective and ATP-competitive pan-Akt inhibitor with IC 50 s of 5, 18 and 8 nM for Akt1, Akt2 and Akt3, respectively.

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Akt1 5 nM (IC50) Akt3 8 nM (IC50

Ipatasertib shows more than 600 and more than 100-fold selectivity for Akt1 in IC50 against the closely related kinases PKA and p70S6K, respectively. When tested at 1 μM in a panel of 230 protein kinases, which includes 36 human AGC family members, Ipatasertib inhibits only 3 other kinases by more than 70% at 1 μM concentration (PRKG1α, PRKG1β, and p70S6K). IC50s measured for these 3 kinases are 98, 69, and 860 nM, respectively. Thus, with the exception of PKG1 (relative to which Ipatasertib is >10-fold more selective for Akt1), Ipatasertib displays a more than 100-fold selectivity for Akt1 over the next most potently inhibited non-Akt kinase, p70S6K, in the screening kinase panel. The relationship between pharmacokinetics (PK) and pharmacodynamics (PD) of Ipatasertib is investigated in 3 xenograft models that showed dose-dependent response to drug tre

Ipatasertib is typically efficacious in xenograft models in which Akt is activated because of genetic alterations including PTEN loss, PIK3CA mutations/amplifications, or HER2 overexpression. In these models, tumor growth delay, stasis, or regression is achieved at or below 100 mg/kg daily oral dose, which is the maximum dose tested in immunocompromised mice that is well tolerated. When tested in vivo, daily dosing of Ipatasertib in combination with RP-56976 induces tumor regression and stasis in the PC-3 and MCF7-neo/HER2 xenograft models, at doses where each single agent is ineffective or only causes modest tumor growth delay. Similarly, increased TGI is observed in the OVCAR3 ovarian cancer xenograft model when Ipatasertib is combined with NSC 241240. The combination of Ipatasertib with RP-56976 or NSC 241240 is tolerated with less than 5% body weight loss when compared wit

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]. Blake JF, et al. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J Med Chem. 2012 Sep 27;55(18):8110-27.
[2]. Lin J, et al. Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models. Clin Cancer Res. 2013 Apr 1;19(7):1760-72.

In Vitro: DMSO : 100 mg/mL (188.35 mM; Need ultrasonic)H₂O : ≥ 41 mg/mL (77.22 mM)