GSK2636771

Catalog No.S8002 Batch:S800203

Technical Data

Formula

C₂₂H₂₂F₃N₃O₃

Molecular Weight

433.42

CAS No.

1372540-25-4

Solubility (25°C)*

In vitro

DMSO

54 mg/mL (124.59 mM)

Ethanol

6 mg/mL (13.84 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	0.5mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 10 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 clarify; 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.
Clear solution	5% DMSO 1 95% Corn oil	1.0mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

GSK2636771 is a potent, orally bioavailable and selective inhibitor of PI3Kβ with >900-fold selectivity over PI3Kα/PI3Kγ and >10-fold over PI3Kδ. Sensitive to PTEN null cell lines.

Targets

PI3Kβ ^[1]

In vitro

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. ^[1] 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. ^[2]

In vivo

GSK-2636771 decreases phosphorylated protein kinase Akt (Ser473) levels in these xenograft models. GSK-2636771 (100 mg/kg) do not increase glucose/insulin levels in mice. ^[1]

Protocol (from reference)

Cell Assay:^{^[2]}	Cell lines p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines. Concentrations ~10 μM Incubation Time 72 hours Method 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. 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.
Animal Study:^[3]	Animal Models Balb-c nude mice Dosages 100 mg/kg Administration oral administration

Cell Assay:^{^[2]}

Cell lines
p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines.
Concentrations
~10 μM
Incubation Time
72 hours
Method
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. 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.

Animal Study:^[3]

Animal Models
Balb-c nude mice
Dosages
100 mg/kg
Administration
oral administration

References

Customer Product Validation

: , , Clin Cancer Res, 2017, 23(11):2795-2805

: , , Dr. Antonino Maria Spartà from University of Bolog

: Data from [Data independently produced by , , FASEB J, 2018, doi:10.1096/fj.201800183R]

: Data from [Data independently produced by , , Mol Pharmacol, 2016, 90(6):726-737]

Selleck's GSK2636771 has been cited by 16 publications

Idelalisib activates AKT via increased recruitment of PI3Kδ/PI3Kβ to BCR signalosome while reducing PDK1 in post-therapy CLL cells [ Leukemia, 2022, 10.1038/s41375-022-01595-0]	PubMed: 35568768
PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury [ Cells, 2022, 11(21)3515]	PubMed: 36359913
Computational analysis of cholangiocarcinoma phosphoproteomes identifies patient-specific drug targets [ Cancer Res, 2021, canres.0955.2021]	PubMed: 34551960
Cisplatin Resistance in Osteosarcoma: In vitro Validation of Candidate DNA Repair-Related Therapeutic Targets and Drugs for Tailored Treatments. [ Front Oncol, 2020, 10;10:331]	PubMed: 32211337
Targeting effector pathways in RAC1P29S-driven malignant melanoma. [ Small GTPases, 2020, 10.1080/21541248]	PubMed: 32043900
Tumor Suppressor miRNA-204-5p Regulates Growth, Metastasis, and Immune Microenvironment Remodeling in Breast Cancer. [ Cancer Res, 2019, 79(7):1520-1534]	PubMed: 30737233
Amphiregulin potentiates airway inflammation and mucus hypersecretion induced by urban particulate matter via the EGFR-PI3Kα-AKT/ERK pathway [Wang J, et al. Cell Signal, 2019, 53:122-131]	PubMed: 30291869
Prostate-specific membrane antigen cleavage of vitamin B9 stimulates oncogenic signaling through metabotropic glutamate receptors. [ J Exp Med, 2018, 215(1):159-175]	PubMed: 29141866
PI3Ka-Akt1-mediated Prdm4 induction in adipose tissue increases energy expenditure, inhibits weight gain, and improves insulin resistance in diet-induced obese mice [ Cell Death Dis, 2018, 9(9):876]	PubMed: 30158592
Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy [Saintigny P, et al. Cancer, 2018, 124(18):3693-3705]	PubMed: 30289966

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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