Biological Activity

Bioactivity / Mechanism

GSK690693 altered AKT-pathway signaling in primary Lck-MyrAkt2 lymphoma cultures. At 10 μM for 8 h, downstream Gsk3 and PRAS40/Akt1s1 phosphorylation decreased while Akt phosphorylation increased. This cellular readout does not establish exclusive target selectivity. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target	Activity	Value
Akt1	IC50	2nM
PKCη	IC50	2nM
PKCθ	IC50	2nM
PrkX	IC50	5nM
Akt3	IC50	9nM
Akt2	IC50	13nM
PKCδ	IC50	14nM
PKCβ	IC50	19nM
PKCε	IC50	21nM
PKA	IC50	24nM
PKG1β	IC50	33nM

11 targets · Scroll to view more

Cellular Effect

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

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In Vitro Studies

In the pediatric cancer cell-line panel, 96 h GSK690693 exposure produced a median viability IC50 of 1.2 μM. COG-LL-317 was highly sensitive (6.5 nM), whereas five cell lines had IC50 values >10 μM. Sensitivity therefore varied substantially by model. [2]

AKT-pathway signaling in primary murine lymphoma cultures

Cell-based study · Thymic lymphoma cultures 55–228, 55–2180 and 55–1143 from Lck-MyrAkt2 mice [1]

Immunoblots showed reduced phosphorylation of downstream pathway proteins while phospho-Akt increased. This high-concentration cellular experiment does not establish exclusive AKT selectivity.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Phosphorylated Gsk3α/β and Akt1s1/PRAS40; phospho-Akt	Qualitative immunoblot response Downstream phosphorylation decreased; phospho-Akt increased	[1]

Literature-Reported Treatment Conditions

Treatment concentration: 10 μM
Exposure duration: 8 h
Method: Western blot analysis versus DMSO control
Vehicle: DMSO
Co-treatment: Single agent
Reported limits: Final DMSO percentage and exact independent biological replicate count not specified; methods state blots were confirmed in at least duplicate or triplicate runs.

Methods and source locations

Compound reported in the paper: GSK690693

Published experiments with GSK-supplied material; no validation of an Adooq lot or equivalence between formulations.

Figure 2B; Results paragraph beginning “Since various human tumor cell lines”; Materials and Methods: Reagents, Cell Culture, Western Blot Analysis

Phosphorylated Gsk3α/β and Akt1s1/PRAS40; phospho-Akt: Paired untreated/treated lanes with corresponding total proteins and β-actin loading control; no numerical densitometry extracted. — Figure 2B; Results paragraph beginning “Since various human tumor cell lines”; Materials and Methods: Reagents, Cell Culture, Western Blot Analysis

Pediatric cancer cell-line sensitivity panel

Cell-based study · PPTP pediatric cancer cell-line panel, including ALL, AML, sarcoma and neuroblastoma models [2]

Sensitivity varied widely after 96 h exposure. Cellular viability IC50 values are assay endpoints, not biochemical potency or animal doses.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Viable-cell response across the panel	Median IC50 1.2 μM	[2]
Sensitive and resistant cell-line responses	IC50 COG-LL-317: 6.5 nM; five cell lines: >10 μM	[2]

Literature-Reported Treatment Conditions

Treatment concentration: 1 nM to 10 μM
Exposure duration: 96 h
Method: DIMSCAN fluorescein-diacetate viable-cell assay
Co-treatment: Single agent
Reported limits: In-vitro vehicle concentration and exact replicate number are not specified in the acquired main methods. Figure 1 expresses viability relative to controls; Table I additionally includes relative input/output measures.

Methods and source locations

Compound reported in the paper: GSK690693

Published experiments with GSK-supplied material; no validation of an Adooq lot or equivalence between formulations.

Materials and Methods: In Vitro Testing; Results: GSK690693 in Vitro Testing; Table I and Figure 1

Viable-cell response across the panel: DIMSCAN; reported panel median in Results. — Materials and Methods: In Vitro Testing; Results: GSK690693 in Vitro Testing; Table I and Figure 1

Sensitive and resistant cell-line responses: Results rounded value for COG-LL-317; Table I reports 6.49 × 10−9. No curve-derived decimals. — Materials and Methods: In Vitro Testing; Results: GSK690693 in Vitro Testing; Table I and Figure 1

In Vivo Studies

GSK690693 showed limited single-agent activity in the pediatric xenograft panel at 30 mg/kg intraperitoneally, once daily on a 5-days-on/2-days-off schedule for 6 weeks. No objective responses occurred. Some solid tumor models showed EFS differences, but treated mice had more deaths than controls, and five models were excluded for excessive toxicity. [2]

Limited activity in the primary pediatric xenograft panel

Animal study · 42 evaluable pediatric xenograft models; five additional models excluded for excessive toxicity [2]

No objective responses occurred. Some EFS differences were detected, but intermediate EFS activity was limited to KT-12 and OS-33. Mortality and excluded models limit interpretation.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Objective response and EFS	Response / EFS distribution No objective responses; significant EFS differences: 12/34 solid tumor models and 0/8 ALL models	[2]
Deaths during primary testing	Observed mortality GSK690693: 43/450 (9.6%); controls: 3/445 (0.7%)	[2]

Conditions shared by the study groups

Route: Intraperitoneal
Frequency: Once daily, 5 days on and 2 days off
Treatment course: 6 weeks
Vehicle: 5% (w/v) mannitol in saline

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Primary GSK690693 xenograft panel 30 mg/kg	Control arms; Figure 2 identifies vehicle-treated controls. Intended groups: 10 mice for solid tumors or 8 for leukemias.	No objective responses in evaluable solid tumor or ALL panels. Significant EFS differences in 12/34 evaluable solid tumor models; none of 8 ALL models. Treated-group deaths: 43/450; controls: 3/445 across primary testing.	[2]

Primary GSK690693 xenograft panel: Model: Pediatric solid tumor xenografts in female CB17SC-M scid mice or BALB/c nu/nu mice (glioma); ALL xenografts in female NOD/scid mice.; Reported limits: Actual per-model enrollment and exclusions in Supplementary Table I were not retrieved. Death counts are study totals, not restricted to evaluable models.

Methods and source locations

Compound reported in the paper: GSK690693

Published experiments with GSK-supplied material; no validation of an Adooq lot or equivalence between formulations.

Materials and Methods: In Vivo Tumor Growth Inhibition Studies, Summary statistics and analysis methods, Statistical Methods, Drugs and Formulation; Results: Activity of GSK690693 Against the PPTP In Vivo Panel; Table II and Figure 3

Objective response and EFS: Objective response defined as PR, CR or maintained CR; EFS differences versus controls assessed by exact log-rank tests. — Materials and Methods: In Vivo Tumor Growth Inhibition Studies, Summary statistics and analysis methods, Statistical Methods, Drugs and Formulation; Results: Activity of GSK690693 Against the PPTP In Vivo Panel; Table II and Figure 3

Deaths during primary testing: Main Results totals; five models excluded for excessive toxicity. — Materials and Methods: In Vivo Tumor Growth Inhibition Studies, Summary statistics and analysis methods, Statistical Methods, Drugs and Formulation; Results: Activity of GSK690693 Against the PPTP In Vivo Panel; Table II and Figure 3

Primary GSK690693 xenograft panel · Materials and Methods: In Vivo Tumor Growth Inhibition Studies, Summary statistics and analysis methods, Statistical Methods, Drugs and Formulation; Results: Activity of GSK690693 Against the PPTP In Vivo Panel; Table II and Figure 3

Specifications

Manufacturer	Adooq Bioscience
Actions	Inhibitor
CAS Number	937174-76-0
Applications	AKT inhibitor
Formula	C₂₁H₂₇N₇O₃
Molecular Weight	425.5
SMILES	CCN1C2=C(C(=NC=C2OC[C@H]3CCCNC3)C#CC(C)(C)O)N=C1C4=NON=C4N

Storage & Solubility

In Vitro Solubility

Reported Solubility

Solvent	Reported Solubility
DMSO	36 mg/mL (84.61 mM)
Water	Insoluble
Ethanol	Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration: 2 mg/mL
Vehicle: 5% DMSO+40%PEG300+5% tween80+50% H2O

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

[1] Deborah A Altomare, Lili Zhang, Jing Deng, et al. GSK690693 Delays Tumor Onset and Progression in Genetically-Defined Mouse Models Expressing Activated Akt Clinical cancer research : an official journal of the American Association for Cancer Research (2010). PMID: 20075391 DOI: 10.1158/1078-0432.CCR-09-1026 Source material
[2] Hernan Carol, Christopher L Morton, Richard Gorlick, et al. Initial Testing (Stage 1) of the Akt Inhibitor GSK690693 by the Pediatric Preclinical Testing Program Pediatric blood & cancer (2010). PMID: 20740623 DOI: 10.1002/pbc.22710 Source material

Publications

1 publication citing this product

Khan MI, .et al. , Prog Neuropsychopharmacol Biol Psychiatry, 2018, Mar 2;82:39-48 PMID: 9223784

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GSK690693

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Biological Activity

Bioactivity / Mechanism

Target & Activity

Cellular Effect

In Vitro Studies

AKT-pathway signaling in primary murine lymphoma cultures

Literature-Reported Treatment Conditions

Pediatric cancer cell-line sensitivity panel

Literature-Reported Treatment Conditions

In Vivo Studies

Limited activity in the primary pediatric xenograft panel

Conditions shared by the study groups

Specifications

Storage & Solubility

In Vitro Solubility

Reported Solubility

Preparing Stock Solutions

In Vivo Preparation

Storage

Research References

Publications

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