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Chemical Structure| 937174-76-0 Chemical Structure| 937174-76-0
Chemical Structure| 937174-76-0

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CAS No.: 937174-76-0

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

Synonyms: GSK-690693

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Product Details of GSK-690693

CAS No. :937174-76-0
Formula : C21H27N7O3
M.W : 425.48
SMILES Code : CC(O)(C)C#CC1=NC=C(OC[C@@H]2CNCCC2)C3=C1N=C(C4=NON=C4N)N3CC
Synonyms :
GSK-690693
MDL No. :MFCD14105605
InChI Key :KGPGFQWBCSZGEL-ZDUSSCGKSA-N
Pubchem ID :16725726

Safety of GSK-690693

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of GSK-690693

PI3K-AKT

Isoform Comparison

Biological Activity

Target

  • Akt3

    Akt3, IC50:9 nM

  • Akt1

    Akt1, IC50:2 nM

  • Akt2

    Akt2, IC50:13 nM

In Vitro:

Cell Line
Concentration Treated Time Description Reference
PC3-LN4 cells 5 μM 24 h GSK690693 markedly increased the levels of Pim-1 protein but had a minimal effect on the expression of Pim-3 protein and reduced the levels of Pim-2. PMC3680595
PC3-LN4 cells 5 μM 24 h GSK690693 increased the level of Pim-1 mRNA but not Pim-2 or Pim-3 mRNA. PMC3680595
PC3-LN4 cells 5 μM 24 h GSK690693 increased the protein levels of multiple RTKs, including MET, EPHA2, RON, EGFR, HER2, HER3, INSR, and IGF1R. PMC3680595
Thymic lymphoma cells 0, 10 or 20 μM 72 h To evaluate the effect of GSK-690693 on apoptosis, results showed that GSK-690693 induced a 2-3 fold increase in apoptosis within 24 h. PMC2807995
MOVCAR5 and MOVCAR6 cells 0, 10 or 20 μM 72 h To evaluate the effect of GSK-690693 on the cell cycle, results showed that MOVCAR5 cells exhibited ~50% increase in cell cycle arrest in G1 phase. PMC2807995
143B cells 10 μM 72 h GSK690693 attenuated the chemoresistance induced by ZIP10 overexpression PMC8549349
SW1990 1 mM 72 h GSK690693 significantly alleviated the adenosine-induced p21 upregulation and augmented Akt phosphorylation via a negative feedback loop. PMC6796568
BxPC-3 1 mM 72 h GSK690693 significantly alleviated the adenosine-induced p21 upregulation and augmented Akt phosphorylation via a negative feedback loop. PMC6796568
WEHI-231 cells 10 μM 30 min Inhibition of PI3K signaling pathway PMC7913714
143B cells 10 μM 72 h GSK690693 attenuated the chemoresistance induced by ZIP10 overexpression. PMC8549349
A549 cells 5.93 μM 24 h Evaluate the Akt inhibitory effect of GSK-690693 on A549 cells, showing an IC50 value of 5.93 μM. PMC9916685
Thymic lymphoma cells 10 μM 8 h To detect the inhibitory effect of GSK690693 on phosphorylation of downstream targets of the Akt signaling pathway PMC2807995
Ovarian cancer cells 10 μM Overnight To detect the inhibitory effect of GSK690693 on phosphorylation of downstream targets of the Akt signaling pathway PMC2807995

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description Reference
Mice AOM/DSS-induced CAC model Intraperitoneal injection 30 mg/kg Three times a week for two weeks GSK-690693 inhibited the promoting effect of 5-HT on tumor growth PMC9131283
nude mice PC3-LN4 xenograft model intraperitoneal injection 30 mg/kg daily for 21 days GSK690693 alone caused a modest inhibition of tumor growth, but the combined treatment with the Pim inhibitor SMI-4a resulted in a markedly greater inhibition of tumor growth. PMC3680595
Mice Lck-MyrAkt2 transgenic mice, Pten+/- knockout mice, TgMISIIR-TAg-DR26 transgenic mice Intraperitoneal injection 30 mg/kg Once daily, 5 days per week, for 4 weeks To evaluate the effect of GSK-690693 on tumor development, results showed that GSK-690693 delayed tumor development and reduced tumor size in various mouse models. PMC2807995
Mice KrasG12D-driven skin cancer model Intraperitoneal injection 30 mg/kg Daily for 10 days GSK690693 had only a small effect on SCC tumor regression, even at a dose that markedly reduced Akt signaling activity. PMC3500416
nude mice 143B cell xenograft model intraperitoneal injection 30 mg/kg once daily for 30 days GSK690693 attenuated the tumor growth and chemoresistance induced by ZIP10 overexpression PMC8549349
mice orthotopic pancreatic cancer model intraperitoneal injection 20 mg/kg every other day for 6 weeks GSK690693 further enhanced the therapeutic effect of adenosine on pancreatic cancer, reducing tumor volume and increasing caspase-3 activation. PMC6796568
nude mice xenograft tumor model intraperitoneal injection 30 mg/kg once daily for 30 days GSK690693 attenuated the tumor growth and chemoresistance induced by ZIP10 overexpression. PMC8549349
Mice Lck-MyrAkt2 transgenic mice Intraperitoneal injection 30 mg/kg Once daily, 5 days per week, for 4 weeks To evaluate the efficacy of GSK690693 in delaying tumor development and reducing tumor size PMC2807995

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00493818 Cancer Phase 1 Terminated - United States, Indiana ... More >> GSK Investigational Site Indianapolis, Indiana, United States, 46202 United States, Michigan GSK Investigational Site Detroit, Michigan, United States, 48201 United States, North Carolina GSK Investigational Site Durham, North Carolina, United States, 27710 Less <<
NCT00666081 Cancer Phase 1 Withdrawn(Study Cancelled befo... More >>re enrollment) Less << December 2009 -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.35mL

0.47mL

0.23mL

11.75mL

2.35mL

1.18mL

23.50mL

4.70mL

2.35mL

References

 

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