GSK-690693

Name: GSK-690693
Brand: MedChemExpress
SKU: HY-10249
Rating: 5.0 (31 reviews)

Cat. No.: HY-10249 Purity: 98.46%: FAQs
Data Sheet SDS COA Handling Instructions

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GSK-690693 is an ATP-competitive pan-Akt inhibitor with IC₅₀s of 2 nM, 13 nM, 9 nM for Akt1, Akt2 and Akt3, respectively. GSK-690693 is also an AMPK inhibitor, affects Unc-51-like autophagy activating kinase 1 (ULK1) activity and robustly inhibits STING-dependent IRF3 activation.

For research use only. We do not sell to patients.

GSK-690693 Chemical Structure

CAS No. : 937174-76-0

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 132	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 132	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 120	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 169	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 338	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 540	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 865	In-stock	Estimated Time of Arrival: December 31
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Customer Review

Based on 31 publication(s) in Google Scholar

Other Forms of GSK-690693:

AKT Kinase Inhibitor In-stock

31 Publications Citing Use of MCE GSK-690693

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View All Isoforms

Akt Akt1 Akt2 Akt3

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NUAK1 NUAK2 AMPK AMPK α1β1γ1 AMPK α2β1γ1 AMPK α1β2γ1 AMPK α2β2γ1

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target^[1]

Akt1

2 nM (IC₅₀)

Akt3

9 nM (IC₅₀)

Akt2

13 nM (IC₅₀)

PKCη

2 nM (IC₅₀)

PKCθ

2 nM (IC₅₀)

PrkX

5 nM (IC₅₀)

PAK6

6 nM (IC₅₀)

PAK4

10 nM (IC₅₀)

PKCδ

14 nM (IC₅₀)

PKCβ1

19 nM (IC₅₀)

PKCε

21 nM (IC₅₀)

PKA

24 nM (IC₅₀)

PKG1β

33 nM (IC₅₀)

AMPK

50 nM (IC₅₀)

PAK5

52 nM (IC₅₀)

DAPK3

81 nM (IC₅₀)

Autophagy

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	105.33 μM Compound: GSK690693	Cytotoxicity against human A549 cells assessed as decrease in cell viability after 24 hrs by MTT assay Cytotoxicity against human A549 cells assessed as decrease in cell viability after 24 hrs by MTT assay	[PMID: 29966916]
C6	IC₅₀	14.5 μM Compound: GSK690693	Cytotoxicity against rat C6 cells assessed as decrease in cell viability after 24 hrs by MTT assay Cytotoxicity against rat C6 cells assessed as decrease in cell viability after 24 hrs by MTT assay	[PMID: 29966916]
HCT-116	IC₅₀	8.2 μM Compound: GSK690693	Growth inhibition of human HCT116 cells after 72 hrs by coulter counter method Growth inhibition of human HCT116 cells after 72 hrs by coulter counter method	[PMID: 24900862]
JeKo-1	IC₅₀	3 μM Compound: GSK690693	Antiproliferative activity against human JeKo1 cells after 72 hrs by CellTiter Glo assay Antiproliferative activity against human JeKo1 cells after 72 hrs by CellTiter Glo assay	[PMID: 28704757]
JVM-2	IC₅₀	1.6 μM Compound: GSK690693	Antiproliferative activity against human JVM2 cells after 72 hrs by CellTiter Glo assay Antiproliferative activity against human JVM2 cells after 72 hrs by CellTiter Glo assay	[PMID: 28704757]
Maver1	IC₅₀	5.1 μM Compound: GSK690693	Antiproliferative activity against human Maver1 cells after 72 hrs by CellTiter Glo assay Antiproliferative activity against human Maver1 cells after 72 hrs by CellTiter Glo assay	[PMID: 28704757]
NCI-H460	IC₅₀	5.4 μM Compound: GSK690693	Growth inhibition of human NCI-H460 cells after 72 hrs by coulter counter method Growth inhibition of human NCI-H460 cells after 72 hrs by coulter counter method	[PMID: 24900862]
PC-3	IC₅₀	14.1 μM Compound: GSK690693	Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay	[PMID: 30151089]
PC-3	IC₅₀	15.5 μM Compound: GSK690693	Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay	[PMID: 24308997]
Z-138	IC₅₀	3.1 μM Compound: GSK690693	Antiproliferative activity against human Z138 cells after 72 hrs by CellTiter Glo assay Antiproliferative activity against human Z138 cells after 72 hrs by CellTiter Glo assay	[PMID: 28704757]

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

425.48

Formula

C₂₁H₂₇N₇O₃

CAS No.

937174-76-0

Appearance

Solid

Color

Light yellow to yellow

SMILES

CC(O)(C)C#CC1=NC=C(OC[C@@H]2CNCCC2)C3=C1N=C(C4=NON=C4N)N3CC

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Solvent & Solubility

In Vitro:

DMSO : 20 mg/mL (47.01 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : 5 mg/mL (11.75 mM; ultrasonic and adjust pH to 5 with HCl)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.3503 mL	11.7513 mL	23.5026 mL
5 mM	0.4701 mL	2.3503 mL	4.7005 mL
10 mM	0.2350 mL	1.1751 mL	2.3503 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.88 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 2

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2 mg/mL (4.70 mM); Clear solution; Need ultrasonic

This protocol yields a clear solution of 2 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 3

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2 mg/mL (4.70 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 20% HP-β-CD/10 mM Citrate pH 2.0
Solubility: 10 mg/mL (23.50 mM); Clear solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 98.46%

Select Batch:

Data Sheet (284 KB) SDS (420 KB)

COA (251 KB) RP-HPLC (247 KB)

Handling Instructions (2659 KB)

References

[1]. Rhodes N, et al. Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity. Cancer Res, 2008, 68(7), 2366-2374. [Content Brief]

[2]. Levy DS, et al. AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines. Blood, 2009, 113(8), 1723-1729. [Content Brief]

[3]. Altomare DA, et al. GSK690693 delays tumor onset and progression in genetically defined mouse models expressing activated Akt. Clin Cancer Res, 2010, 16(2), 486-496. [Content Brief]

[4]. Konno H, et al. Pro-inflammation Associated with a Gain-of-Function Mutation (R284S) in the Innate Immune Sensor STING. Cell Rep. 2018 Apr 24;23(4):1112-1123. [Content Brief]

Kinase Assay ^[1]	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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[1]	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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Tumors are initiated by injection of tumor cell suspension (HCC1954, MDA-MB-453, and LNCaP) or tumor fragments (BT474, SKOV-3, and PANC1) s.c. in 8- to 12-wk-old CD1 Swiss Nude mice (LNCaP, SKOV-3, and PANC1) or SCID mice (HCC1954, MDA-MB-453, and BT474). When tumors reach a volume of 100 to 200 mm³, mice are randomized and divided into groups of 8 to 12 mice per group. GSK690693 is administered once daily at 10, 20, and 30 mg/kg by i.p. administration. Animals are euthanized by inhalation of CO₂ at the completion of the study. Tumor volume is measured twice weekly by calipers, using the equation: tumor volume (mm³)=(length × width²)/2. Results are reported as % inhibition on day 21 of treatment=100× [1-(average growth of the drug-treated population/average growth of vehicle-treated control population)]. Statistical analysis is done using two-tailed t test. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Rhodes N, et al. Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity. Cancer Res, 2008, 68(7), 2366-2374. [Content Brief] [2]. Levy DS, et al. AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines. Blood, 2009, 113(8), 1723-1729. [Content Brief] [3]. Altomare DA, et al. GSK690693 delays tumor onset and progression in genetically defined mouse models expressing activated Akt. Clin Cancer Res, 2010, 16(2), 486-496. [Content Brief] [4]. Konno H, et al. Pro-inflammation Associated with a Gain-of-Function Mutation (R284S) in the Innate Immune Sensor STING. Cell Rep. 2018 Apr 24;23(4):1112-1123. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

H₂O / DMSO	1 mM	2.3503 mL	11.7513 mL	23.5026 mL	58.7566 mL
	5 mM	0.4701 mL	2.3503 mL	4.7005 mL	11.7513 mL
	10 mM	0.2350 mL	1.1751 mL	2.3503 mL	5.8757 mL
DMSO	15 mM	0.1567 mL	0.7834 mL	1.5668 mL	3.9171 mL
	20 mM	0.1175 mL	0.5876 mL	1.1751 mL	2.9378 mL
	25 mM	0.0940 mL	0.4701 mL	0.9401 mL	2.3503 mL
	30 mM	0.0783 mL	0.3917 mL	0.7834 mL	1.9586 mL
	40 mM	0.0588 mL	0.2938 mL	0.5876 mL	1.4689 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

GSK-690693 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

GSK-690693937174-76-0GSK690693GSK 690693AktAMPKAutophagyPKBProtein kinase BAMP-activated protein kinaseInhibitorinhibitorinhibit

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GSK-690693

Customer Review

Other Forms of GSK-690693:

GSK-690693 Related Antibodies

31 Publications Citing Use of MCE GSK-690693

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All Akt Isoform Specific Products:

View All AMPK Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

GSK-690693 Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

GSK-690693 Related Classifications

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