1. PI3K/Akt/mTOR
  2. Akt

GDC-0068 (Synonyms: Ipatasertib; RG7440)

Cat. No.: HY-15186 Purity: >98.0%
Data Sheet SDS Handling Instructions

GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1/Akt2/Akt3 with IC50 of 5/18/8 nM, 620-fold selectivity over PKA.

For research use only. We do not sell to patients.
GDC-0068 Chemical Structure

GDC-0068 Chemical Structure

CAS No. : 1001264-89-6

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $99 In-stock
5 mg $90 In-stock
10 mg $120 In-stock
50 mg $350 In-stock
100 mg $650 In-stock
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500 mg   Get quote  

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Other Forms of GDC-0068:

    GDC-0068 purchased from MCE. Usage Cited in: Oncotarget. 2016 May 17;7(20):29131-42.

    A674563 selectively inhibits FLT3-ITD. Inhibitory Effects of A674563 against auto-phosphorylation of FLT3 wt/mt kinases in the FLT3 wt/mt transformed BaF3 isogenic cell lines.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1/Akt2/Akt3 with IC50 of 5/18/8 nM, 620-fold selectivity over PKA.

    IC50 & Target

    IC50: 5±7 nM (Akt1), 18±10 nM (Akt2), 8±9 nM (Akt3), 3100±705 nM (PKA)[1]

    In Vitro

    GDC-0068 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, GDC-0068 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 GDC-0068 is >10-fold more selective for Akt1), GDC-0068 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 GDC-0068 is investigated in 3 xenograft models that showed dose-dependent response to drug treatment: MCF7-neo/HER2, TOV-21G.x1, and LNCaP. The mean cell viability IC50 of GDC-0068 in these 3 cell lines is 2.56, 0.44, and 0.11 μM, respectively[2].

    In Vivo

    GDC-0068 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 GDC-0068 in combination with Docetaxel 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 GDC-0068 is combined with Carboplatin. The combination of GDC-0068 with Docetaxel or Carboplatin is tolerated with less than 5% body weight loss when compared with treatment with each chemotherapeutic agent alone[2].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.1834 mL 10.9170 mL 21.8341 mL
    5 mM 0.4367 mL 2.1834 mL 4.3668 mL
    10 mM 0.2183 mL 1.0917 mL 2.1834 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [2]

    GDC-0068 is prepared in DMSO and stored, and then diluted with appropriate medium before use[2].

    The 384-well plates are seeded with 2,000 cells per well in a volume of 54 μL per well followed by incubation at 37°C under 5% CO2 overnight (~16 hours). Compounds (e.g., GDC-0068) are diluted in DMSO to generate the desired stock concentrations then added in a volume of 6 μL per well. All treatments are tested in quadruplicates. After 4 days incubation, relative numbers of viable cells are estimated using CellTiter-Glo and total luminescence is measured on a Wallac Multilabel Reader. The concentration of drug resulting in IC50 is calculated from a 4-parameter curve analysis (XLfit) and is determined from a minimum of 3 experiments. For cell lines that failed to achieve an IC50, the highest concentration tested (10 μM) is listed[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    GDC-0068 is formulated in 0.5% methylcellulose/0.2% Tween-80 (MCT)[2].

    Mice[2]
    In vivo efficacy is evaluated in multiple tumor cell line- and patient-derived xenograft models. Cells or tumor fragments are implanted subcutaneously into the flank of immunocompromised mice. Female or male nude (nu/nu) or severe combined immunodeficient mice (SCID)/beige mice are used. For the MCF7-neo/HER2 model, 17β-estradiol pellets (0.36 mg/pellet, 60-day release) are implanted into the dorsal shoulder before cell inoculation. The LuCaP35V patient-derived primary tumors are obtained; male mice are castrated before implantation of tumor fragments. After implantation of tumor cells or fragments into mice, tumors are monitored until they reached mean tumor volumes of 180 to 350 mm3 and distributed into groups of 8 to 10 animals/group. GDC-0068 is formulated in 0.5% methylcellulose/0.2% Tween-80 (MCT) and administered daily (QD), via oral (per os; PO) gavage. Docetaxel is formulated in 3% EtOH/97% saline and dosed intravenously (IV) every week (QW) at 2.5 or 7.5 mg/kg. Carboplatin is formulated in saline and dosed intraperitoneally (IP) weekly at 50 mg/kg. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    458.0

    Formula

    C₂₄H₃₂ClN₅O₂

    CAS No.

    1001264-89-6

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 28 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: >98.0%

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    GDC-0068
    Cat. No.:
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