| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
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Purity: ≥98%
| Targets |
PI3Kβ (Ki = 0.89 nM); PI3Kβ (IC50 = 5.2 nM)
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| ln Vitro |
GSK2636771 is a potent, selective and oral inhibitor of PI3Kβ with aKiof 0.89 nM and an IC50 of 5.2 nM, showing 900-fold selectivity over p110α and p110γ, and 10-fold selectivity over p110δ isoforms.Cell Assay: Cells (p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines)are plated in 96-well microtiter plates at densities ranging from 1,500 to 15,000 cells/well, optimized for untreated control cells to be 80-90% confluent at the endpoint of the experiment. After 24 h, cells are treated with serial dilutions (100pM to 10μM) of GSK2636771. Cell viability is assessed after 72 h of treatment by incubation with CellTiter Blue for 1.5 h. The drug concentration requires for survival of 50% of cells relative to untreated cells (surviving fraction 50, SF50) is determined using GraphPad Prism version 5.0d. Cell lines that fails to achieve the SF50 to a given drug are nominally assigned as the highest concentration screened (i.e. 10μM). At least three independent experiments in triplicate per cell line targeted drug are performed. Association between a mutation and response to a targeted agent is determined using a Fisher’s exact test (GraphPad Prism), and a two-tailed P value<0.05 is considered statistically significant.GSK-2636771 shows selectively inhibitory activity in PTEN null cell lines (human prostate adenocarcinoma PC-3 and breast cancer HCC70) with EC50 of 36 nM and 72 nM, respectively.GSK2636771 significantly decreases cell viability in p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines, and leads to a marked decrease of AKT phosphorylation only in the control prostate and breast cancer cell lines.
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| ln Vivo |
GSK2636771 is a p110β inhibitor, and the p110β prepares cells to react to stimulation by growth factors. Dual targeting of p110α/β enhances apoptosis and provides sustained tumor response in mice model, whereas p110β inhibition inhibits cell and tumor growth[2].
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| Cell Assay |
Cells are plated in 96-well microtiter plates at densities ranging from 1,500 to 15,000 cells/well, optimized for untreated control cells to be 80-90% confluent at the endpoint of the experiment. After 24 h, cells are treated with serial dilutions (100pM to 10μM) of GSK2636771. Cell viability is assessed after 72 h of treatment by incubation with CellTiter Blue for 1.5 h. The drug concentration requires for survival of 50% of cells relative to untreated cells (surviving fraction 50, SF50) is determined using GraphPad Prism version 5.0d. Cell lines that fails to achieve the SF50 to a given drug are nominally assigned as the highest concentration screened (i.e. 10μM). At least three independent experiments in triplicate per cell line targeted drug are performed. A Fisher's exact test (GraphPad Prism) is used to determine whether a mutation and response to a targeted agent are associated, and a two-tailed P value of 0.05 is regarded as statistically significant.
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| Animal Protocol |
Balb-c nude mice
100 mg/kg oral administration |
| References |
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| Molecular Formula |
C22H22F3N3O3
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|---|---|
| Molecular Weight |
433.42
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| Exact Mass |
433.16133
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| Elemental Analysis |
C, 60.96; H, 5.12; F, 13.15; N, 9.69; O, 11.07
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| CAS # |
1372540-25-4
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| Related CAS # |
1372540-25-4;2108806-07-9 (HCl);1372540-91-4 (tris);
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| Appearance |
white solid powder
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| SMILES |
O=C(C1=C2C(N(CC3=CC=CC(C(F)(F)F)=C3C)C(C)=N2)=CC(N4CCOCC4)=C1)O
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| InChi Key |
XTKLTGBKIDQGQL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H22F3N3O3/c1-13-15(4-3-5-18(13)22(23,24)25)12-28-14(2)26-20-17(21(29)30)10-16(11-19(20)28)27-6-8-31-9-7-27/h3-5,10-11H,6-9,12H2,1-2H3,(H,29,30)
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| Chemical Name |
2-methyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazole-4-carboxylic acid.
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| Synonyms |
GSK 2636771; GSK2636771; GSK-2636771
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~28 mg/mL (64.6 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3072 mL | 11.5362 mL | 23.0723 mL | |
| 5 mM | 0.4614 mL | 2.3072 mL | 4.6145 mL | |
| 10 mM | 0.2307 mL | 1.1536 mL | 2.3072 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04439188 | Active Recruiting |
Drug: PI3K-beta Inhibitor GSK2636771 | Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) | February 25, 2016 | Phase 2 |
| NCT04439149 | Active Recruiting |
Drug: PI3K-beta Inhibitor GSK2636771 | Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) | February 25, 2016 | Phase 2 |
| NCT03131908 | Active Recruiting |
Drug: GSK2636771 Drug: Pembrolizumab |
Melanoma and Other Malignant Neoplasms of Skin Metastatic Melanoma |
M.D. Anderson Cancer Center | July 17, 2017 | Phase 1 Phase 2 |
| NCT04439188 | Active Recruiting |
Drug: PI3K-beta Inhibitor GSK2636771 | Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) | February 25, 2016 | Phase 2 |
| NCT02465060 | Active Recruiting |
Drug: Adavosertib Drug: Afatinib |
Bladder Carcinoma Breast Carcinoma |
National Cancer Institute (NCI) | August 12, 2015 | Phase 2 |
Clin Cancer Res. 2013, 19(13), 3533-3544. |
PI3K inhibition-induced Rb inactivation predicts subsequent apoptosis in PTEN-deficient, ER+ breast cancer cells.Clin Cancer Res.2017 Jun 1;23(11):2795-2805. |
PI3K inhibition-induced Rb inactivation predicts subsequent apoptosis in PTEN-deficient, ER+ breast cancer cells.Clin Cancer Res.2017 Jun 1;23(11):2795-2805. |
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