Free shipping on all orders over $ 500

GDC-0068

Cat. No. M1862
GDC-0068 Structure
Synonym:

Ipatasertib, RG7440

Size Price Availability Quantity
10mg USD 170 In stock
50mg USD 480 In stock
100mg USD 650 In stock
Bulk Inquiry?

Quality Control
Biological Activity

GDC-0068 (RG7440) is a novel, ATP-competitive and orally bioavailable Akt inhibitor with IC50 values of 5 nM, 18 nM and 8 nM for Akt1, Akt2 and Akt3, respectively. Ipatasertib (GDC-0068) demonstrates potent inhibition of all three Akt isoforms in biochemical assays, but poor inhibition of other AGC family kinases. Moreover, GDC-0068 selectively inhibits cell cycle progression and viability of cancer cell lines driven by PI3K/Akt signaling pathway, including those with defects in the tumor suppressor PTEN, oncogenic mutations in PIK3CA, and amplification of HER2. GDC-0068 (Ipatasertib) blocks the phosphorylation of multiple downstream targets of Akt in human cancer cell lines. GDC-0068 (RG7440) shows good oral exposure resulting in dose-dependent pharmacodynamic effects on downstream biomarkers and a robust anti-tumor response in xenograft models in which the PI3K-Akt-mTOR pathway is activated.

Protocol
Cell Experiment
Cell lines MCF10A cells with or without PTEN knockout (KO)
Preparation method Cell viability assays The 384-well plates were 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 were diluted in dimethyl sulfoxide (DMSO) to generate the desired stock concentrations then added in a volume of 6 μL per well. All treatments were tested in quadruplicates. After 4 days incubation, relative numbers of viable cells were estimated using CellTiter-Glo (Promega) and total luminescence was measured on a Wallac Multilabel Reader (PerkinElmer). The concentration of drug resulting in IC50 was calculated from a 4-parameter curve analysis (XLfit, IDBS software) and was determined from a minimum of 3 experiments. For cell lines that failed to achieve an IC50, the highest concentration tested (10 μmol/L) is listed.
Concentrations 0~10µM
Incubation time 4 days
Animal Experiment
Animal models MCF7-neo/HER2 tumor xenograft model
Formulation 0.5% methylcellulose/0.2% Tween-80 (MCT)
Dosages 0,12.5, 25, 50, 75, 100mg/kg
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 458
Formula C24H32ClN5O2
CAS Number 1001264-89-6
Purity 99.76%
Solubility DMSO ≥90 mg/mL
Ethanol ≥90 mg/mL
Storage at -20°C
References

Discovery and Preclinical Pharmacology of a Selective ATP-competitive Akt Inhibitor (GDC-0068) for the Treatment of Human Tumors.
Blake et al. J Med Chem. 2012 Aug 30. PMID: 22934575.

Related Akt Products
Uprosertib (GSK2141795)

GSK2141795 is a potent and selective pan-Akt inhibitor with IC50 values of 180 nM for Akt1, 328 nM for Akt2, and 38 nM for Akt3 respectively (Clinical phase 1).

GDC-0068 (dihydrochloride)

GDC-0068(RG 7440) 2Hcl is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM, 620-fold selectivity over PKA.

Afuresertib

Afuresertib (GSK2110183) is a potent, orally bioavailable Akt inhibitor with Ki of 0.08 nM, 2 nM, and 2.6 nM for Akt1, Akt2, and Akt3, respectively. Phase 2.

SC79

SC79 is an inhibitor of Akt-PH domain translocation and a specific Akt activator used to enhance Akt activity in various conditions.

AKT inhibitor VIII

Akt Inhibitor VIII is a cell-permeable quinoxaline compound that has been shown to potently, selectively, allosterically, and reversibly inhibit Akt1, Akt2, and Akt3 activity (IC50 = 58 nM, 210 nM, and 2.12 μM; respectively).

  Catalog
Abmole Inhibitor Catalog 2017




Keywords: GDC-0068, Ipatasertib, RG7440 supplier, Akt, inhibitors

Contact Us

Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.