Name: GSK690693
Brand: Selleck Chemicals
SKU: S1113
Availability: InStock
Rating: 5 (125 reviews)

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Quality Control

Batch: Purity: 99.09%

99.09

Related Targets	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Other Akt Inhibitors	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Ipatasertib (GDC-0068) Perifosine Triciribine (API-2) Afuresertib (GSK2110183) CCT128930 Akti-1/2 A-674563 HCl

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
LNCaP	Proliferation assay		Antiproliferative activity against human LNCaP cells, IC50=20 nM	18800763
BT474	Proliferation assay		Antiproliferative activity against human BT474 cells, IC50=50 nM	18800763
Sf9	Function assay		Inhibition of human recombinant ROCK1 expressed in Sf9 cells, IC50=0.89 μM	18800763
NCI-H460	Growth inhibition assay	72 h	Growth inhibition of human NCI-H460 cells after 72 hrs by coulter counter method, IC50=5.4 μM	24900862
PC3	Proliferation assay	72 h	Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay, IC50=15.5 μM	24308997
HFF	Cytotoxic assay		Cytotoxicity against HFF cells, IC50=16.3 μM	18800763
LNCAP	Antiproliferative assay		Antiproliferative activity against human LNCAP cells, IC50 = 0.021 μM.	19179070
BT474	Antiproliferative assay		Antiproliferative activity against human BT474 cells, IC50 = 0.069 μM.	19179070
BT474	Function assay		Inhibition of GSK3-beta phosphorylation in human BT474 cells, IC50 = 0.138 μM.	19179070
JVM2	Antiproliferative assay	72 hrs	Antiproliferative activity against human JVM2 cells after 72 hrs by CellTiter Glo assay, IC50 = 1.6 μM.	28704757
JeKo1	Antiproliferative assay	72 hrs	Antiproliferative activity against human JeKo1 cells after 72 hrs by CellTiter Glo assay, IC50 = 3 μM.	28704757
Z138	Antiproliferative assay	72 hrs	Antiproliferative activity against human Z138 cells after 72 hrs by CellTiter Glo assay, IC50 = 3.1 μM.	28704757
SP49	Antiproliferative assay	72 hrs	Antiproliferative activity against human SP49 cells after 72 hrs by CellTiter Glo assay, IC50 = 4.8 μM.	28704757
Maver1	Antiproliferative assay	72 hrs	Antiproliferative activity against human Maver1 cells after 72 hrs by CellTiter Glo assay, IC50 = 5.1 μM.	28704757
C6	Function assay	24 hrs	Inhibition of Akt in rat C6 cells after 24 hrs by ELISA, IC50 = 6.97 μM.	29966916
C6	Cytotoxicity assay	24 hrs	Cytotoxicity against rat C6 cells assessed as decrease in cell viability after 24 hrs by MTT assay, IC50 = 14.5 μM.	29966916
A549	Function assay	24 hrs	Inhibition of Akt in human A549 cells after 24 hrs by ELISA, IC50 = 17.33 μM.	29966916
Mino	Antiproliferative assay	72 hrs	Antiproliferative activity against human Mino cells after 72 hrs by CellTiter Glo assay, IC50 = 20.8 μM.	28704757
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
MCL	Antiproliferative assay	24 hrs	Antiproliferative activity against primary human MCL cells up to 60 uM after 24 hrs by CellTiter Glo assay	28704757
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 21 mg/mL (49.35 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.000mg/ml (7.05mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	425.48	Formula	C₂₁H₂₇N₇O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	937174-76-0	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CCN1C2=C(C(=NC=C2OCC3CCCNC3)C#CC(C)(C)O)N=C1C4=NON=C4N

Mechanism of Action

Targets/IC₅₀/Ki	ULK1 STING AMPK Akt1 (Cell-free assay) 2 nM PKCη (Cell-free assay) 2 nM PKCθ (Cell-free assay) 2 nM PrkX (Cell-free assay) 5 nM Akt3 (Cell-free assay) 9 nM Akt2 (Cell-free assay) 13 nM PKCδ (Cell-free assay) 14 nM PKCβ (Cell-free assay) 19 nM PKCε (Cell-free assay) 21 nM PKA (Cell-free assay) 24 nM PKG1β (Cell-free assay) 33 nM
In vitro	GSK690693 is very selective for the Akt isoforms versus the majority of kinases in other families. However, this compound 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. It 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. This chemical inhibits the phosphorylation of GSK3β in tumor cells with IC50 ranging from 43 nM to 150 nM. Its treatment leads to a dose-dependent increase in the nuclear accumulation of the transcription factor FOXO3A. This compound 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. Its treatment induces apoptosis at concentrations >100 nM in both LNCaP and BT474 cells. Consistent with the role of AKT in cell survival, it induces apoptosis in sensitive ALL cell lines.
Kinase Assay	In vitro kinase assays
Kinase Assay	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.
In vivo	A single administration of GSK690693 inhibits GSK3β phosphorylation in human breast carcinoma (BT474) xenografts in a dose- and time-dependent manner. Similarly, this compound induces a reduction in phosphorylation of the Akt substrates, PRAS40, and FKHR/FKHRL1. It also results in an acute increase in blood glucose, returning to baseline 8 to 10 hours after drug administration. Administration of this chemical 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. This compound exhibits efficacy irrespective of the mechanism of Akt activation involved. It is most effective in delaying tumor progression in Lck-MyrAkt2 mice expressing a membrane-bound, constitutively active form of Akt.
References	[1] https://pubmed.ncbi.nlm.nih.gov/18381444/ [2] https://pubmed.ncbi.nlm.nih.gov/19064730/ [3] https://pubmed.ncbi.nlm.nih.gov/20075391/ [4] https://pubmed.ncbi.nlm.nih.gov/29694889/

Applications

Methods	Biomarkers	Images	PMID
Western blot	pPRAS40 / PRAS40 / pBAD / BAD p-Akt / Akt / p-GSK3 / p-mTOR / mTOR / p-p70S6K / p-FoxO3a / p-FoxO1		25551293
Growth inhibition assay	Cell viability		20075391

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00666081	Withdrawn	Cancer	GlaxoSmithKline	April 2008	Phase 1
NCT00493818	Terminated	Cancer	GlaxoSmithKline	April 2007	Phase 1

Tech Support

Handling Instructions

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

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Frequently Asked Questions

Question 1:
Why did pAKT increase after treatment with it?

Answer:
It actually inhibits AKT, but does not necessarily decrease p-Akt level. Treatment with this compound 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.

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):

GSK690693 pan-Akt Inhibitor

Chemical Structure

Molecular Weight: 425.48