1. PI3K/Akt/mTOR
  2. mTOR
    PI3K

GDC-0084 (Synonyms: RG7666)

Cat. No.: HY-19962 Purity: 99.54%
Data Sheet SDS Handling Instructions

GDC-0084 is a brain penetrant inhibitor of PI3K and mTOR, with Kis of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively.

For research use only. We do not sell to patients.
GDC-0084 Chemical Structure

GDC-0084 Chemical Structure

CAS No. : 1382979-44-3

Size Price Stock Quantity
10 mM * 1 mL in DMSO $93 In-stock
1 mg $60 In-stock
5 mg $110 In-stock
10 mg $160 In-stock
50 mg $540 In-stock
100 mg $950 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Featured Recommendations

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

GDC-0084 is a brain penetrant inhibitor of PI3K and mTOR, with Kis of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively.

IC50 & Target

Ki: 2 nM (PI3Kα), 46 nM (PI3Kβ), 3 nM (PI3Kδ), 10 nM (PI3Kγ), 70 nM (mTOR)[1]

In Vitro

GDC-0084 (Compound 16) maintains inhibition of each of the Class I PI3K isoforms but with more potent inhibition of mTOR. GDC-0084 is also tested in five different GBM cell lines and is found to have antiproliferative EC50s ranging from 0.3 to 1.1 μM[1].

In Vivo

After a 25 mg/kg dose of GDC-0084 (Compound 16) administered orally, pAKT in normal mouse brain tissue is significantly inhibited at 1 and 6 h postdose. The potent inhibition of pAKT at both time points in this study demonstrates that GDC-0084 inhibits its target behind a fully intact BBB. In addition to the pharmacodynamic effect in normal brain tissue, GDC-0084 is studied in a subcutaneous U87 tumor xenograft model of glioblastoma in mice. In this study, GDC-0084 achieves significant and dose-dependent tumor growth inhibition. Tumor growth inhibition is first observed at a 2.2 mg/kg dose level. Higher doses led to greater tumor growth inhibition, including tumor regressions at the 17.9 mg/kg dose level. Each of these doses is well tolerated for the duration of the study[1].

Clinical Trial
View MoreCollapse
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.6149 mL 13.0746 mL 26.1493 mL
5 mM 0.5230 mL 2.6149 mL 5.2299 mL
10 mM 0.2615 mL 1.3075 mL 2.6149 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[1]

Enzymatic activity of PI3Kα is measured using a fluorescence polarization assay that monitors formation of the product 3,4,5-inositoltriphosphate molecule (PIP3) as it competes with fluorescently labeled PIP3 for binding to the GRP-1 pleckstrin homology domain protein. An increase in phosphatidyl inositide-3-phosphate product results in a decrease in fluorescence polarization signal as the labeled fluorophore is displaced from the GRP-1 protein binding site. PI3Kα is expressed and purified as heterodimeric recombinant protein. PI3Kα is assayed under initial rate conditions in the presence of 10 mM Tris (pH 7.5), 25 uM ATP, 9.75 uM PIP2, 5% glycerol, 4 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 2% (v/v) DMSO at a 60 ng/mL concentration of PI3Kα. After assay for 30 min at 25°C, reactions are terminated with a final concentration of 9 mM EDTA, 4.5 nM TAMRA-PIP3, and 4.2 ug/mL GRP-1 detector protein before reading fluorescence polarization on an Envision plate reader. IC50s are calculated from the fit of the dose-response curves to a 4-parameter equation. Apparent Kis, where measured, are determined at a fixed concentration of ATP near the measured Km for ATP for PI3Kα, and are calculated by fitting of the dose-response curves to an equation for tightbinding competitive inhibition[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

GDC-0084 (Compound 16) is formulated once weekly in 0.5% methylcellulose and 0.2% Tween-80 (Mice)[1].

Mice[1]
PTEN-null U-87 MG/M human glioblastoma cancer cells are cultured in RPMI 1640 media plus 1% L-glutamine with 10% fetal bovine serum. Cells in log-phase growth are harvested and resuspended in HBSS:Matrigel (1:1, v:v) for injection into female NCr nude mice aged 20 weeks. Animals receive five million cells subcutaneously in the right lateral thorax in 0.1 mL. Mice bearing established tumors in the range of 200-500 mm3 are separated into groups of equally sized tumors (n=6-7/group) to receive escalating doses of GDC-0084 (Compound 16). GDC-0084 is formulated once weekly in 0.5% methylcellulose and 0.2% Tween-80 at concentrations needed for target doses in a volume of 0.2 mL. All formulations are stored in a refrigerator and brought to room temperature and mixed well by vortex before oral administration by gavage once daily for 23 days. Tumor volumes are calculated. Changes in body weights are reported as a percentage change from the starting weight.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

382.42

Formula

C₁₈H₂₂N₈O₂

CAS No.

1382979-44-3

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: 6 mg/mL (Need ultrasonic)

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

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
GDC-0084
Cat. No.:
HY-19962
Quantity: