Sign In | Join Free | My xpandrally.com
China abmole limited logo
abmole limited
ICP Remarked Supplier
Home >

Small Molecules (Inhibitors) GDC-0349

Small Molecules (Inhibitors) GDC-0349

Country/Region china

Company abmole limited

Categories CAS 101-14-4

Update 2017-06-07 14:10:50

ICP License Issued by the Chinese Ministry

Contact Now

  • Home
  • Small Molecules
  • PI3K/Akt/mTOR
  • mTOR
  • GDC-0349

GDC-0349

Cat. No. M2094

Synonym: RG7603

SizePriceAvailabilityQuantity
10mg$245In stock
50mg$980In stock
Bulk Inquiry?
Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
  • Product Information
Biological Activity

GDC-0349 is a potent small molecule mTOR inhibitor with Ki of 3.8 nM. GDC-0349 inhibits downstream markers of mTOR, including phospho-4EBP1 and phospho-Akt(S473) in an in vivo PK/PD study in mouse, consistent with an inhibition of both mTORC1 and mTORC2 complexes. GDC-0349 inhibits tumor growth in a dose-dependent manner when dosed orally once daily in athymic mice in a MCF7-neo/Her2 tumor xenograft model.

GDC-0349 is also efficacious in other xenograft models, including PC3 (PTEN null) and 786-O (VHL mutant). GDC-0349 is currently in a Phase I clinical trials in the treatment with solid tumors or Non-Hodgkin's lymphoma.

Protocol
Cell Experiment
Cell lines
Preparation methodCompound activity is tested in 10 point dose curves starting at the highest final concentration of 10 uM. They are serially diluted in 100% DMSO prior to further dilution with assay buffer. The reaction mixture (8 uls) containing 0.25 nM mTOR+GBL enzyme, 400 nM GFP-4E-BP1, 8 uM ATP, 50 mM Hepes pH 7.5, 0.01% Tween 20, 10 mM MnCl2, 1 mM EGTA, 1 mM DTT, 1% DMSO (+/- compound) is incubated at room temperature for 30 minutes. 8 uL of solution containing 2 nM Tb-anti-p4E-BP1 antibody & 10 mM EDTA diluted TR-FRET buffer is then added and incubated for 30 minutes to stop the reaction. The plate is scanned with the Envision plate reader. Ki values are calculated in Assay Explorer using the Morrison ATP-competitive tight binding equation for Ki apparent determination.
Concentrations
Incubation time
Animal Experiment
Animal modelsMCF7-neo/Her-2 mouse xenograft breast cancer model
Formulation0.5% methylcellulose/0.2% Tween 80 (MCT)
Dosages10, 20, 30, 40, 50, 60, 70, and 80 mg/kg QD for 24 days
Administrationorally
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied byAnimal 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 Weight452.55
FormulaC24H32N6O3
CAS Number1207360-89-1
Purity>98%
SolubilityDMSO 90 mg/mL
Storageat -20°C
Chemical NameUrea, N-ethyl-N'-[4-[5,6,7,8-tetrahydro-4-[(3S)-3-methyl-4-morpholinyl]-7-(3-oxetanyl)pyrido[3,4-d]pyrimidin-2-yl]phenyl]-
References

Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349.
Pei Z, et al. ACS Med Chem Lett. 2012 Nov 29;4(1):103-7. PMID: 24900569.

Pyrimidoaminotropanes as potent, selective, and efficacious small molecule kinase inhibitors of the mammalian target of rapamycin (mTOR).
Estrada AA, et al. J Med Chem. 2013 Apr 11;56(7):3090-101.


Product Tags:

cas no: 56-89-3

      

endocrine treatment for breast cancer

      

deca durabolin 200 mg ml

      
China Small Molecules (Inhibitors) GDC-0349

Small Molecules (Inhibitors) GDC-0349 Images

Inquiry Cart 0
Send your message to this supplier
 
*From:
*To: abmole limited
*Subject:
*Message:
Characters Remaining: (0/3000)