GSK690693

Catalog No.S1113

GSK690693 Chemical Structure

Molecular Weight(MW): 425.48

GSK690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2 nM/13 nM/9 nM in cell-free assays, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes. Phase 1.

Size Price Stock Quantity  
In DMSO USD 221 In stock
USD 170 In stock
USD 770 In stock
Bulk Discount
Bulk Inquiry

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

Cited by 36 Publications

Purity & Quality Control

Choose Selective Akt Inhibitors

Biological Activity

Description GSK690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2 nM/13 nM/9 nM in cell-free assays, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes. Phase 1.
Targets
Akt1 [1]
(Cell-free assay)		 PKCη [1]
(Cell-free assay)		 PKCθ [1]
(Cell-free assay)		 PrkX [1]
(Cell-free assay)		 Akt3 [1]
(Cell-free assay)
2 nM 2 nM 2 nM 5 nM 9 nM
In vitro

GSK690693 is very selective for the Akt isoforms versus the majority of kinases in other families. However, GSK690693 is less selective for members of the AGC kinase family including PKA, PrkX, and PKC isozymes with IC50 of 24 nM, 5 nM, and 2-21 nM, respectively. GSK690693 also potently inhibits AMPK and DAPK3 from the CAMK family with IC50 of 50 nM and 81 nM, respectively, and PAK4, 5, and 6 from the STE family with IC50 of 10 nM, 52 nM, and 6 nM, respectively. GSK690693 inhibits the phosphorylation of GSK3β in tumor cells with IC50 ranging from 43 nM to 150 nM. GSK690693 treatment leads to a dose-dependent increase in the nuclear accumulation of the transcription factor FOXO3A. GSK690693 potently inhibits the proliferation of T47D, ZR-75-1, BT474, HCC1954, MDA-MB-453, and LNCaP cells with IC50 of 72 nM, 79 nM, 86 nM, 119 nM, 975 nM, and 147 nM, respectively. GSK690693 treatment induces apoptosis at concentrations >100 nM in both LNCaP and BT474 cells. [1] Consistent with the role of AKT in cell survival, GSK690693 induces apoptosis in sensitive ALL cell lines. [2]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human LNCaP cells MmrqVJJwdGmoZYLheIlwdiCjc4PhfS=> NF\3WpdCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFzOR4FRKGOnbHzzMEBKSzVyPUKwJI5O M2PqTlE5QDByN{[z
human BT474 cells NGSwNHVRem:uaX\ldoF1cW:wIHHzd4F6 MkK1RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCEVES3OEBk\WyuczygTWM2OD13MDDuUS=> MV[xPFgxODd4Mx?=
Sf9 cells NV23XVdlTnWwY4Tpc44h[XO|YYm= MmD6TY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCUT1PLNUBmgHC{ZYPz[YQhcW5iU3[5JINmdGy|LDDJR|UxRTBwOEmg{txO M4PYXVE5QDByN{[z
human NCI-H460 cells MlnzS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MVq3NkBp NXvFOFBsT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVkOLLVi0OlAh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IHPveYx1\XJiY3;1cpRmeiCvZYToc4QtKEmFNUC9OU41KM7:TR?= NVXqOng1OjR7MEC4OlI>
human PC3 cells Ml6zVJJwdGmoZYLheIlwdiCjc4PhfS=> NFW0PZk4OiCq MoLnRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCSQ{OgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0yPS53IN88US=> NVjDcHREOjR|MEi5PVc>
HFF cells MUPDfZRwfG:6aXRCpIF{e2G7 NHLsWYZEgXSxdH;4bYNqfHliYXfhbY5{fCCKRl[gZ4VtdHNuIFnDOVA:OTZwMzFOwG0> MUexPFgxODd4Mx?=

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
p-Akt / Akt / p-GSK3 / p-mTOR / mTOR / p-p70S6K / p-FoxO3a / p-FoxO1 ; 

PubMed: 20075391     


Western blot analysis of MOVCAR5, MOVCAR6 and SKOV3 cells treated overnight with 10 μM GSK690693. Representative panels were screened with antibodies against components of the Akt signaling cascade to detect diminished phosphorylation of downstream targets.

pPRAS40 / PRAS40 / pBAD / BAD ; 

PubMed: 25551293     


Effect of AKT inhibitors on phosphorylation of AKT and AKT protein substrates. EBC1 cells were treated with the indicated doses of MK2206 and GSK690693 (top), or GDC0068 (bottom) for 24 hr. Treated cells were lysed and analyzed by immunoblot with the indicated antibodies. Phosphorylation of PRAS40, BAD, and GSK3β was quantified by image densitometry (middle). 

20075391 25551293
Growth inhibition assay
Cell viability ; 

PubMed: 20075391     


Murine ovarian carcinoma cells (MOVCAR5 and MOVCAR6) and control human SKOV3 ovarian tumors cells were treated with various concentrations of GSK690693 for 72 hrs and analyzed for cell viability by MTT assays. The IC50 was ~3 μM GSK690693 for MOVCAR5 and SKOV3 cells, whereas, MOVCAR6 cells did not reach an IC50 with the drug concentrations used in this experiment. Error bars depict total standard deviation among replicate samples. 

20075391
In vivo A single administration of GSK690693 inhibits GSK3β phosphorylation in human breast carcinoma (BT474) xenografts in a dose- and time-dependent manner. Similarly, GSK690693 induces a reduction in phosphorylation of the Akt substrates, PRAS40, and FKHR/FKHRL1. GSK690693 also results in an acute increase in blood glucose, returning to baseline 8 to 10 hours after drug administration. Administration of GSK690693 induces reductions in phosphorylated Akt substrates in vivo, and potently inhibits the growth of human SKOV-3 ovarian, LNCaP prostate, and BT474 and HCC-1954 breast carcinoma xenografts, with maximal inhibition of 58% to 75% at the dose of 30 mg/kg/day. [1] GSK690693 exhibits efficacy irrespective of the mechanism of Akt activation involved. GSK690693 is most effective in delaying tumor progression in Lck-MyrAkt2 mice expressing a membrane-bound, constitutively active form of Akt. [3]

Protocol

Kinase Assay:[1]
+ Expand

In vitro kinase assays:

His-tagged full-length Akt1, 2, or 3 are expressed and purified from baculovirus. Activation is carried out with purified PDK1 to phosphorylate Thr308 and purified MK2 to phosphorylate Ser473. To more accurately measure time-dependent inhibition of Akt, activated Akt enzymes are incubated with GSK690693 at various concentrations at room temperature for 30 minutes before the reaction is initiated with the addition of substrate. Final reaction contains 5 nM to 15 nM Akt1, 2, and 3 enzymes; 2 μM ATP; 0.15 μCi/μL[γ-33P]ATP; 1 μM Peptide (Biotin-aminohexanoicacid-ARKR-ERAYSFGHHA-amide); 10 mM MgCl2; 25 mM MOPS (pH 7.5); 1 mM DTT; 1 mM CHAPS; and 50 mM KCl. The reactions are incubated at room temperature for 45 minutes, followed by termination with Leadseeker beads in PBS containing EDTA (final concentration, 2 mg/mL beads and 75 mM EDTA). The plates are then sealed, the beads are allowed to settle for at least 5 hours, and product formation is quantitated using a Viewlux Imager.
Cell Research:[1]
+ Expand
  • Cell lines: T47D, ZR-75-1, BT474, HCC1954, MDA-MB-453, LNCaP, etc.
  • Concentrations: Dissolved in DMSO, final concentrations ~30 μM
  • Incubation Time: 72 hours
  • Method: Cells are plated at densities that allow untreated cells to grow logarithmically during the course of a 3-day assay. Briefly, cells are plated in 96- or 384-well plates and incubated overnight. Cells are then treated with GSK690693 (ranging from 30 μM-1.5 nM) and incubated for 72 hours. Cell proliferation is measured using the CellTiter Glo reagent. Data are analyzed using the XLFit curve-fitting tool for Microsoft Excel. IC50 values are obtained by fitting data to Eq, 2.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Female CD1 Swiss Nude mice injected with LNCaP, SKOV-3, or PANC1 cells, and C.B-17 SCID mice with HCC1954, MDA-MB-453, or BT474 cells
  • Formulation: Formulated in either 4% DMSO/40% hydroxypropyl-β-cyclodextrin in water (pH 6.0) or 5% dextrose (pH 4.0)
  • Dosages: ~30 mg/kg/day
  • Administration: Administered via i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 39 mg/mL (91.66 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing. 		15mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 425.48
Formula

C21H27N7O3
CAS No. 937174-76-0
Storage powder
in solvent
Synonyms N/A

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

Frequently Asked Questions

  • Question 1:

    Why pAKT increased after treatment of the inhibitor ?

  • Answer:

    GSK690693 actually inhibits AKT, but not necessarily decrease p-Akt level. Treatment with GSK690693 caused AKT hyper phosphorylation which has already been reported in some papers. (For example, http://www.bloodjournal.org/content/113/8/1723.short?sso-checked=true). To test the inhibition of AKT activity, you might have to look at the level of AKT substrates.

selleck catalog

Akt Signaling Pathway Map

Akt Inhibitors with Unique Features

  • Selective Akt Inhibitor

    CCT128930 : AKT2-selective, IC50=6 nM.

  • Most Potent Akt Inhibitor

    AZD5363 : Akt1, IC50=3 nM; Akt2, IC50=8 nM; Akt3, IC50=8 nM.

  • Akt Inhibitor in Clinical Trial

    Ipatasertib (GDC-0068) : Phase II for Prostate Cancer and Gastric Cancer.

  • Newest Akt Inhibitor

    AZD5363 : Potent inhibitor of all isoforms of Akt (Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM, similar to P70S6K/PKA and lower activity towards ROCK1/2.

Related Akt Products

  • Afuresertib (GSK2110183) New

    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.

  • AT13148 New

    AT13148 is an oral, ATP-competitive, multi-AGC kinase inhibitor with IC50 of 38 nM/402 nM/50 nM, 8 nM, 3 nM, and 6 nM/4 nM for Akt1/2/3, p70S6K, PKA, and ROCKI/II, respectively. Phase 1.

  • SC79 New

    SC79 is a brain-penetrable Akt phosphorylation activator and an inhibitor of Akt-PH domain translocation.

  • MK-2206 2HCl

    MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM in cell-free assays, respectively; no inhibitory activities against 250 other protein kinases observed. Phase 2.

    Features:The first allosteric small molecule inhibitor of Akt to enter clinical development.

  • Capivasertib (AZD5363)

    AZD5363 potently inhibits all isoforms of Akt(Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM in cell-free assays, similar to P70S6K/PKA and lower activity towards ROCK1/2. Phase 2.

    Features:Moderate preclinical tolerability, and PD characteristics of an AKT inhibitor. Distinct profile from other AKT inhibitors in clinical development.

  • Ipatasertib (GDC-0068)

    Ipatasertib (GDC-0068) is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM in cell-free assays, 620-fold selectivity over PKA. Phase 2.

  • Perifosine (KRX-0401)

    Perifosine (KRX-0401) is a novel Akt inhibitor with IC50 of 4.7 μM in MM.1S cells, targets pleckstrin homology domain of Akt. Phase 3.

  • A-674563

    A-674563 is an Akt1 inhibitor with Ki of 11 nM in cell-free assays, modest potent to PKA and >30-fold selective for Akt1 over PKC.

    Features:Orally bioavailable compound (achieved by replacing indole of A-443654 with phenyl moiety) and somewhat less selective for Akt over PKA than A-443654.

  • Triciribine

    Triciribine is a DNA synthesis inhibitor, also inhibits Akt in PC3 cell line and HIV-1 in CEM-SS, H9, H9IIIB, U1 cells with IC50 of 130 nM and 20 nM, respectively; does not inhibit PI3K/PDK1; 5000-fold less active in cells lacking adenosine kinase. Phase 1/2.

  • Honokiol

    Honokiol is the active principle of magnolia extract that inhibits Akt-phosphorylation and promotes ERK1/2 phosphorylation. Phase 3.

Tags: buy GSK690693 | GSK690693 supplier | purchase GSK690693 | GSK690693 cost | GSK690693 manufacturer | order GSK690693 | GSK690693 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID