GSK2636771
GSK2636771 is a p110β isoform-specific inhibitor of PIK3 with SF50 more than 1 μM [1].
PI3K (phosphatidylinositol 3-kinase) has 4 catalytic subunits: p110α, β, δ, γ，and δ. PI3K /AKT and related pathways play important roles in cellular growth and survival via internalizing the effects of external growth factors and membrane tyrosine kinases. [2, 3]. Many studies have shown that PI3K is over activated in a variety of cancer cells and inhibition of this pathway have been focused for cancer patients [4].
GSK2636771 is a selective PI3K inhibitor with targeting p110βand has different with the reported GDC-0941 which inhibits all class I PI3K isoforms. In breast cancer cell lines, treatment with GSK2636771 could significantly decrease the phosphorylation of AKT thus inhibits the cell viability. For EEC cell lines with PTEN-mutant, p110β inhibitor GSK2636771 should only combine with p110α selective inhibitor A66 to decrease cell viability [1].
References:
1.Weigelt, B., et al., PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res, 2013. 19(13): p. 3533-44.
2.Costa, C., et al., Measurement of PIP Levels Reveals an Unexpected Role for p110beta in Early Adaptive Responses to p110alpha-Specific Inhibitors in Luminal Breast Cancer. Cancer Cell, 2014. 24(14): p. 00458-9.
3.Schwartz, S., et al., Feedback Suppression of PI3Kalpha Signaling in PTEN-Mutated Tumors Is Relieved by Selective Inhibition of PI3Kbeta. Cancer Cell, 2014. 24(14): p. 00459-0.
4.Slomovitz, B.M. and R.L. Coleman, The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res, 2012. 18(21): p. 5856-64.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 433.42 |
| Cas No. | 1372540-25-4 |
| Formula | C22H22F3N3O3 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥10.83 mg/mL in DMSO |
| Chemical Name | 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid |
| SDF | Download SDF |
| Canonical SMILES | CC1=C(C=CC=C1C(F)(F)F)CN2C(=NC3=C2C=C(C=C3C(=O)O)N4CCOCC4)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
The human endometrioid endometrial cancer (EEC) cell lines harboring PIK3CA and PTEN mutations |
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Preparation method |
The solubility of this compound in DMSO is >10.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1or 10μM for 72h |
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Applications |
GSK2636771 significantly decreased cell viability in p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines, and led to a marked decrease of AKT phosphorylation. |
| Animal experiment [2]: | |
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Animal models |
Balb-c nude mice |
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Dosage form |
Oral, 100 mg/kg |
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Application |
GSK-2636771 decreased phosphorylated protein kinase Akt (Ser473) levels in these xenograft models, and it did not increase glucose/insulin levels in mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Weigelt B., et al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013, 19(13), 3533-3544. [2]. Macauley D,, et al. Drugs Fut, 2012, 37(6), 451. | |
Quality Control & MSDS
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Chemical structure
